Publications by authors named "Riffat Mehboob"

18 Publications

  • Page 1 of 1

Overexpressed Na 1.7 Channels Confer Hyperexcitability to Trigeminal Sensory Neurons of Ca 2.1 Mutant Hemiplegic Migraine Mice.

Front Cell Neurosci 2021 25;15:640709. Epub 2021 May 25.

Department of Neuroscience, International School for Advanced Studies (SISSA), Trieste, Italy.

Trigeminal sensory neurons of transgenic knock-in (KI) mice expressing the R192Q missense mutation in the α1A subunit of neuronal voltage-gated Ca 2.1 Ca channels, which leads to familial hemiplegic migraine type 1 (FHM1) in patients, exhibit a hyperexcitability phenotype. Here, we show that the expression of Na 1.7 channels, linked to pain states, is upregulated in KI primary cultures of trigeminal ganglia (TG), as shown by increased expression of its α1 subunit. In the majority of TG neurons, Na 1.7 channels are co-expressed with ATP-gated P2X3 receptors (P2X3R), which are important nociceptive sensors. Reversing the trigeminal phenotype with selective Ca 2.1 channel inhibitor ω-agatoxin IVA inhibited Na 1.7 overexpression. Functionally, KI neurons revealed a TTX-sensitive inward current of larger amplitude that was partially inhibited by selective Na 1.7 blocker Tp1a. Under current-clamp condition, Tp1a raised the spike threshold of both wild-type (WT) and KI neurons with decreased firing rate in KI cells. Na 1.7 activator OD1 accelerated firing in WT and KI neurons, a phenomenon blocked by Tp1a. Enhanced expression and function of Na 1.7 channels in KI TG neurons resulted in higher excitability and facilitated nociceptive signaling. Co-expression of Na 1.7 channels and P2X3Rs in TGs may explain how hypersensitivity to local stimuli can be relevant to migraine.
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http://dx.doi.org/10.3389/fncel.2021.640709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185157PMC
May 2021

Enhanced Neurokinin-1 Receptor Expression Is Associated with Human Dental Pulp Inflammation and Pain Severity.

Biomed Res Int 2021 5;2021:5593520. Epub 2021 May 5.

University Institute of Public Health, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan.

Substance P (SP) is a peptide involved in many biological processes, including nociception and inflammation. SP has a high affinity for its receptor neurokinin-1 (NK-1R). SP/NK-1R complex plays a major role in the interactions going on during the onset of dental pain and inflammation. . To identify the expression of NK-1R in healthy and inflamed human dental pulp, as well as to identify any association with severity of dental pain. . This case-control study included ten irreversibly inflamed samples of dental pulp, which were extirpated from patients presenting with chief complaint of dental pain due to caries. Ten healthy pulps, extirpated from those teeth which were indicated for extraction due to orthodontic reasons, were used as the control group. Visual analog scale (VAS) and modified McGill Pain Questionnaire were used to assess the characteristic and severity of pain. Immunohistochemical study was performed using monoclonal antibodies against NK-1R. . The results showed that the NK-1R was expressed intensely in patients with higher pain score. The mean pain score in cases was 7.0 ± 2.0. The healthy dental pulps had negative or mild NK-1R staining of +1 intensity. The NK-1R score in cases was 2.4 ± 0.516 and 0.2 ± 0.4216 in controls. There was significant difference in NK-1R score between both groups ( value <0.05). There was a strong positive correlation between the pain score and NK-1R expression score. As the pain increased, the NK-1R expression score was also increased (0.95, value 0.000). . NK-1R is overexpressed in inflamed dental pulp. SP/NK-1R modulation may provide a novel approach for the treatment of pulpal inflammation and pain.
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http://dx.doi.org/10.1155/2021/5593520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121577PMC
May 2021

Elevated Neurokinin-1 Receptor Expression in Uterine Products of Conception Is Associated With First Trimester Miscarriages.

Front Physiol 2020 18;11:554766. Epub 2020 Dec 18.

Department of Physiology and Cell Biology, University of Health Sciences, Lahore, Pakistan.

Background: Miscarriage is a common complication of early pregnancy, mostly occurring in the first trimester. However, the etiological factors and prognostic and diagnostic biomarkers are not well known. Neurokinin-1 receptor (NK-1R) is a receptor of tachykinin peptide substance P (SP) and has a role in various pathological conditions, cancers, but its association with miscarriages and significance as a clinicopathological parameter are not studied. Accordingly, the present study aimed to clarify the localization and expression for NK-1R in human retained products of conception (POC). The role of NK-1R is not known in miscarriages.

Materials And Methods: NK-1R expression was assessed in POC and normal placental tissues by immunohistochemistry. Three- to four-micrometer-thin sections of formalin-fixed paraffin-embedded tissues were used for this purpose. Tissues were processed and then immunohistochemically stained with NK-1R antibody. Brain tissue was used as control for antibody. Protein expression was evaluated using the nuclear labeling index (%). Tissues were counterstained with 3,3'-diaminobenzidine (DAB), and microscopy was performed at 10×, 20×, and 40× magnifications.

Results: Ten human POC tissues and 10 normal placental tissues were studied by immunohistochemistry to demonstrate the localization of NK-1R. The expression of NK-1R protein was high in all the cases of both groups. NK-1R expression showed no notable differences among different cases of miscarriages as well as normal deliveries at full term regardless of the mother's age and gestational age at which the event occurred. Statistically, no difference was found in both groups, which is in agreement with our hypothesis and previous findings.

Conclusion: The expression of NK-1R was similar in all the cases, and it was intense. It shows that dysregulation of NK-1R along with its ligand SP might be involved in miscarriages and also involved in normal delivery. Our results provide fundamental data regarding this anti-NK-1R strategy. Thus, the present study recommends that SP/NK-1R system might, therefore, be considered as an emerging and promising diagnostic and therapeutic strategy against miscarriages. Hence, we report for the first time the expression and localization of NK-1R in POC. We suggest NK-1R antagonist in addition to the immunoglobulins and human chorionic gonadotropin to diagnose and treat spontaneous miscarriages.
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http://dx.doi.org/10.3389/fphys.2020.554766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775504PMC
December 2020

Neuropathological explanation of minimal COVID-19 infection rate in newborns, infants and children - a mystery so far. New insight into the role of Substance P.

J Neurol Sci 2021 01 17;420:117276. Epub 2020 Dec 17.

Lino Rossi Research Center, University of Milan, Milan, Italy. Electronic address:

Sars-Cov-2 or Novel coronavirus infection (COVID-19) has become a global challenge, affecting elderly population at large, causing a burden on hospitals. It has been affecting the world from a health and economic perspective after its emergence since October 2019 at Wuhan province of China. Later on it became a pandemic, with aged people most affected. Surprisingly, the infants and children were not severely infected and mortality among them was reported infrequently. If they died it was due to some comorbidity or congenital heart problems. Why the rate of infection varies in different age groups around the world and what is the protective mechanism in children remains a mystery. Based on our neuropathological experience at the "Lino Rossi Research Center for the study and prevention of the unexpected perinatal death and Sudden Infant Death Syndrome (SIDS)" of the University of Milan, Italy, we hypothesize that the decreased severity of the disease in infants compared to the elderly may be due to alteration at neurotransmitter levels especially of the Substance P (SP) and of the spinal trigeminal nucleus in the brainstem that is responsible for its secretion. This neurotransmitter may be directly related to the respiratory illness as is in COVID-19 infection. It is responsible for the increased inflammation and the characteristic symptoms associated with this disease. It is the main switch that must be urgently turned off using the NK-1R antagonist which is the receptor of SP and responsible for its functionality, especially in the elderly.
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http://dx.doi.org/10.1016/j.jns.2020.117276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834711PMC
January 2021

Immunohistochemical Expression of the Alpha Nicotinic Acetylcholine Receptor 7 in the Human Normal, Diabetic, and Preeclamptic Placenta and Products of Conception.

Front Physiol 2020 25;11:607239. Epub 2020 Nov 25.

Physiology and Cell Biology Department, University of Health Sciences Lahore, Lahore, Pakistan.

Preeclampsia (PE) and gestational diabetes (GD) are complications in advanced pregnancy while miscarriage for early pregnancy. However, the etiological factors are not well understood. Smoking has been associated with these complications as well as the sudden intrauterine deaths, sudden infant death, miscarriages, and still births. However, the immunolocalization of alpha 7 nicotine acetylcholine receptor (α7-nAChR) is not studied. α7-nAChR subunit expression was evaluated in 10 paraffin-embedded placental tissues after delivery and 10 tissue samples of products of conception during first trimester by immunohistochemistry. Among the placental tissues, two samples were normal placental tissue, four from PE mother, and four from GD mother. The expression of α7-nAChR was compared between the two groups in general and within the subgroups of placenta as well. Protein expression was evaluated using the nuclear labeling index (%) of villi with positive cells stained, positive cells in the decidua, and intensity of staining in the outer villous trophoblast layer. The expression of α7-nAChR protein was high in all the cases of placenta and products of conception (POCs). α7-nAChR expression showed no notable differences among different cases of miscarriages irrespective of the mother's age and gestational age at which the event occurred. However, there were some changes among the normal, PE, and GD placental groups in the linings of the blood vessels. Changes were restricted to the villi (as opposed to the decidua) lining cells, both cytotrophoblast and syncytiotrophoblast, and were specific to the α7 subunit. PE blood vessel lining was thicker and showed more expression of this receptor in endothelial cells and myofibroblasts in PE and GD groups. In POCs, the strong expression was observed in the decidua myocytes of maternal blood vessels and in syncytiotrophoblast and cytotrophoblast of chronic villi. Nicotine acetyl choline receptors are found to be expressed highly in the placental tissues and in products of conception. They may be associated with the sudden perinatal deaths and miscarriages or complications of pregnancy.
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http://dx.doi.org/10.3389/fphys.2020.607239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724587PMC
November 2020

Substantia Nigra Abnormalities Provide New Insight on the Neural Mechanisms Underlying the Sleep-Arousal Phase Dysfunctions in Sudden Infant Death Syndrome.

ASN Neuro 2020 Jan-Dec;12:1759091420962695

"Lino Rossi" Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.

The purpose of this study was to research possible developmental alterations of the substantia nigra (SN) in sudden infant death syndrome (SIDS), a syndrome frequently attributed to arousal failure from sleep. Brain stems of 46 victims of sudden infant death, aged from 1 to about 7 months (4 to 30 postnatal weeks), were investigated. Twenty-six of these cases were diagnosed as SIDS, due to the lack of any pathological finding, while the remaining 20 cases in which the cause of death was determined at autopsy served as controls. Maternal smoking was reported in 77% of SIDS and 10% of controls. Histopathological examination of the SN was done on 5-µm-thick sections of caudal midbrain stained with both hematoxylin-eosin and Klüver-Barrera. Densitometry, immunohistochemistry and histochemistry were applied to highlight the neuronal concentration, the tyrosine hydroxylase (TH) expression, and the presence of neuromelanin (NM) in this structure. Hypoplasia of the pars compacta portion of the SN was observed in 69% of SIDS but never in controls; TH expression was significantly higher in controls than in SIDS; and NM was observed only in 4 infants of the control group but not in SIDS. A significant correlation was found between SIDS, hypoplasia/low neuronal density, low TH expression in the pars compacta, and maternal smoking. Because the SN pars compacta, being the major dopamine brain center, controls many functions, including the sleep-arousal phase, its alterations, especially concurrently with smoking exposure, may contribute to explain the pathogenesis of SIDS that occur in the great part of cases at awakening from sleep.
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http://dx.doi.org/10.1177/1759091420962695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545522PMC
September 2021

Diagnostic accuracy of carotid intima media thickness by B-mode ultrasonography in coronary artery disease patients.

Arch Med Sci Atheroscler Dis 2020 27;5:e79-e84. Epub 2020 May 27.

University Institute of Radiological Sciences and Medical Imaging Technology, University of Lahore, Lahore, Pakistan.

Introduction: Cardiovascular diseases (CVD) are the main cause of premature deaths worldwide, and atherosclerosis (AS) is a major risk factor associated with them. B-mode ultrasound is a well-validated research tool that has been translated increasingly into clinical practice. The aim of the study was to assess the diagnostic accuracy of carotid intima media thickness by B-mode ultrasonography in coronary artery disease patients.

Material And Methods: This was a case control study, including 100 cases and the same number of controls. Patients with positive angiographic findings and chest pain were considered as cases and those without as negative. Duplex carotid ultrasound was used to detect intima-media thickness (IMT). B-mode real-time ultrasonic images were obtained with a 7 MHz transducer. An intima media thickness of 0.6 mm was considered as being without plaque.

Results: The angiographic findings were single-vessel disease, double-vessel disease, and triple-vessel disease in 18%, 11.5%, and 20.5% of cases, respectively, while there were no findings in controls. There was plaque formation in 14.5% and calcification in 12% of the cases. Sensitivity of B-mode ultrasonography was found to be 78%, specificity 75%, positive predictive value 75.72%, and negative predictive value 77.31%.

Conclusions: Carotid ultrasonography can be utilised as a valuable screening tool due to having several advantages, including ease of application, reproducibility, low cost, and strong correlation with atherosclerosis.
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http://dx.doi.org/10.5114/amsad.2020.95651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277461PMC
May 2020

Extensively Drug-Resistant (XDR) Typhoid: Evolution, Prevention, and Its Management.

Biomed Res Int 2020 2;2020:6432580. Epub 2020 May 2.

Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan.

Typhoid fever is the result of a human host-restricted serotype typhi infection that causes enteric fever. Around 21 million people contract typhoid annually, with Pakistan's inhabitants at most risk amongst Asian countries where typhoid remains prevalent. Decades of indiscriminate antibiotic usage has driven the evolution of multidrug-resistant strains and more recently, extensively drug-resistant (XDR) strains of serotype typhi. Current reports of extensively drug-resistant typhoid fever outbreak in Pakistan are not only a major concern for Pakistan but also for health authorities worldwide: intercontinental transmission, spread, and replacement of native strains in neighboring countries and a major impediment to Pakistani health care management. The WHO records that there are 5274 cases of extensively drug-resistant (XDR) typhoid fever out of a total of 8188 total cases of typhoid fever reported in Pakistan. The last remaining feasible oral antibiotic that XDR typhoid remains susceptible to is azithromycin; this is a cause of major concern. Additionally, several cases of XDR typhoid fever have also been reported in patients travelling from Pakistan to the USA, UK, and Canada. This review article attempts to raise the issue of XDR typhoid with respect to its epidemiology, prevention, management, and future outlook and stresses a better understanding of antimicrobial stewardship and general surveillance of the disease. Although progress is being made to combat XDR typhoid locally, efficient, unified efforts on a national and international scale are required to contain the XDR outbreak before it is no longer manageable and leads us back to the preantibiotic era.
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http://dx.doi.org/10.1155/2020/6432580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212280PMC
February 2021

Sonographic Presentation of the Geyser Sign.

Case Rep Med 2019 31;2019:5623530. Epub 2019 Oct 31.

Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan.

A case of geyser sign with acromioclavicular (AC) joint cyst with underlying rotator cuff tear is presented. Ultrasound modality is used to diagnose the clinical case of the AC cyst with positive geyser sign. A 91-year-old male patient presented with a complaint of right-sided shoulder and neck pain. The physical examination revealed a large lump on his right shoulder with restricted shoulder movements. During ultrasound examination, a chronic supraspinatus tendon (ST) tear and AC joint cyst with a positive geyser sign was observed. The ultrasound diagnosis was also confirmed with magnetic resonance imaging (MRI). AC joint cyst with geyser sign is a rare condition. Few cases have been published with this type of pathology. To our knowledge, this is the first report of its kind from Pakistani population.
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http://dx.doi.org/10.1155/2019/5623530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875333PMC
October 2019

Neurochemical Alterations in Sudden Unexplained Perinatal Deaths-A Review.

Front Pediatr 2018 25;6. Epub 2018 Jan 25.

Research Unit, Faculty of Allied Health Sciences, University of Lahore, Lahore, Pakistan.

Sudden unexpected perinatal collapse is a major trauma for the parents of victims. Sudden infant death syndrome (SIDS) is unexpected and mysterious death of an apparently healthy neonate from birth till 1 year of age without any known causes, even after thorough postmortem investigations. However, the incidence of sudden intrauterine unexplained death syndrome (SIUDS) is seven times higher as compared with SIDS. This observation is approximated 40-80%. Stillbirth is defined as death of a fetus after 20th week of gestation or just before delivery at full term without a known reason. Pakistan has the highest burden of stillbirth in the world. This basis of SIDS, SIUDS, and stillbirths eludes specialists. The purpose of this study is to investigate factors behind failure in control of these unexplained deaths and how research may go ahead with improved prospects. Animal models and physiological data demonstrate that sleep, arousal, and cardiorespiratory malfunctioning are abnormal mechanisms in SIUDS risk factors or in newborn children who subsequently die from SIDS. This review focuses on insights in neuropathology and mechanisms of SIDS and SIUDS in terms of different receptors involved in this major perinatal demise. Several studies conducted in the past decade have confirmed neuropathological and neurochemical anomalies related to serotonin transporter, substance P, acetylcholine α7 nicotine receptors, etc., in sudden unexplained fetal and infant deaths. There is need to focus more on research in this area to unveil the major curtain to neuroprotection by underlying mechanisms leading to such deaths.
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http://dx.doi.org/10.3389/fped.2018.00006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788892PMC
January 2018

Towards Better Understanding of the Pathogenesis of Neuronal Respiratory Network in Sudden Perinatal Death.

Front Neurol 2017 6;8:320. Epub 2017 Jul 6.

Biomedical Sciences, King Edward Medical University, Lahore, Pakistan.

Sudden perinatal death that includes the victims of sudden infant death syndrome, sudden intrauterine death syndrome, and stillbirth are heartbreaking events in the life of parents. Most of the studies about sudden perinatal death were reported from Italy, highlighting two main etiological factors: prone sleeping position and smoking. Other probable contributory factors are prematurity, male gender, lack of breastfeeding, respiratory tract infections, use of pacifiers, infant botulism, extensive use of pesticides and insecticides, etc. However, extensive studies across the world are required to establish the role of these factors in a different subset of populations. Previous studies confirmed the widely accepted hypothesis that neuropathology of the brainstem is one of the main cause of sudden perinatal death. This study is an effort to summarize the neuropathological evaluation of the brainstems and their association to sudden perinatal death. Brainstem nuclei in vulnerable infants undergo certain changes that may alter the sleep arousal cycle, cardiorespiratory control, and ultimately culminate in death. This review focuses on the roles of different brainstem nuclei, their pathologies, and the established facts in this regard in terms of it's link to such deaths. This study will also help to understand the role of brainstem nuclei in controlling the cardiorespiratory cycles in sudden perinatal death and may provide a better understanding to resolve the mystery of these deaths in future. It is also found that a global initiative to deal with perinatal death is required to facilitate the diagnosis and prevention in developed and as well as developing countries.
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http://dx.doi.org/10.3389/fneur.2017.00320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498558PMC
July 2017

Characterization and Expression of Sphingosine 1-Phosphate Receptors in Human and Rat Heart.

Front Pharmacol 2017 24;8:312. Epub 2017 May 24.

Cardiac Surgery Division, University of Verona Medical SchoolVerona, Italy.

Sphingosine 1-phosphate (S1P), sphingolipid derivatives are known anti-inflammatory, anti-apoptotic, and anti-oxidant agent. S1P have been demonstrated to have a role in the cardiovascular system. The purpose of this study was to understand the precise expression and distribution of S1P receptors (S1PRs) in human and rat cardiovascular tissues to know the significance and possible implementation of our experimental studies in rat models. In this study, we investigated the localization of S1PRs in human heart samples from cardiac surgery department, University of Verona Hospital and rat samples. Immunohistochemical investigation of paraffin-embedded sections illustrated diffused staining of the myocardial samples from human and rat. The signals of the human heart were similar to those of the rat heart in all chambers of the heart. The immunohistochemical expression levels correlated well with the results of RT-PCR-based analysis and western blotting. We confirmed by all techniques that S1PR1 expressed strongly as compared to S1PR3, and are uniformly distributed in all chambers of the heart with no significant difference in human and rat myocardial tissue. S1PR2 expression was significantly weak while S1PR4 and S1PR5 were not detectable in RT-PCR results in both human and rat heart. These results indicate that experimental studies using S1PR agonists on rat models are more likely to have a potential for translation into clinical studies, and second important information revealed by this study is, S1P receptor agonist can be used for cardioprotection in global ischemia-reperfusion injury.
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http://dx.doi.org/10.3389/fphar.2017.00312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442178PMC
May 2017

Substance P/Neurokinin 1 and Trigeminal System: A Possible Link to the Pathogenesis in Sudden Perinatal Deaths.

Authors:
Riffat Mehboob

Front Neurol 2017 13;8:82. Epub 2017 Mar 13.

Biomedical Sciences, King Edward Medical University , Lahore , Pakistan.

Sudden demise of a healthy fetus or a neonate is a very tragic episode in the life of parents. These deaths have been a mystery since ages but still remain unexplained. This review proposes the involvement of trigeminal nerve, neurotransmitter substance P (SP), and its receptor neurokinin 1 (NK-1R) in regulation of cardiorespiratory control in fetuses and newborns. Anomalies and immaturity of neuroregulatory systems such as trigeminal system in medulla oblongata of brainstem may provide a possible mechanism of sudden perinatal deaths. Vulnerable infants are born with respiratory center immaturity which in combination with any stressor such as cold, hypoxia, and smoking may lead to cessation of breathing and ventilatory response. SP/NK-1R may be involved in regulating the ventilatory control in neonates while it is decreased in fetal and adult life in humans, and any alterations from these may lead to irreversible sleep apnea and fatal breathing, ultimately sudden death. This review summarizes the studies performed to highlight the expression of SP or NK-1R in sudden perinatal deaths and proposes the involvement of trigeminal ganglion along with its nerve and SP/NK-1R expression alteration as one of the possible pathophysiological underlying mechanism. However, further studies are required to explore the role of SP, NK-1R, and trigeminal system in the pathogenesis of sudden infant deaths, sudden intrauterine deaths, stillbirths, and sudden deaths later in human life.
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http://dx.doi.org/10.3389/fneur.2017.00082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346962PMC
March 2017

Role of neurotransmitter Substance P in progression of oral squamous cell carcinoma.

Pathol Res Pract 2015 Mar 13;211(3):203-7. Epub 2014 Oct 13.

Department of Biomedical Sciences, King Edward Medical University, Lahore, Pakistan.

Background: Oral squamous cell carcinoma (OSCC) is the most frequent type of head and neck cancers.

Objectives: In the present study, we evaluated the expression and distribution of Substance P (SP) in different grades of OSCC and role of SP in its proliferation and progression.

Subjects And Methods: Forty OSCC biopsies were immunohistochemically analyzed by using SP antibody, including 29 male and 11 female cases. 35% were well differentiated, 35% moderately differentiated and 30% poorly differentiated OSCC. The majority of patients were in the age range of 41-80 years. 62% of the cases were positive for SP. SP positivity was expressed in the cytoplasm of the tumor cells. Most of the positive cases were from the tongue region.

Results: 93% of moderately differentiated, 92% of poorly differentiated and 8% of well-differentiated carcinomas were SP-positive, but SP expression intensity was highest in poorly differentiated cases (+3). More positive patients were males (68.96% of all male patients) with moderately and poorly differentiated OSCC. Among all positive cases, 48% were poorly differentiated, 48% moderately differentiated and 4% well differentiated.

Conclusion: Strong expression of SP in poorly and moderately differentiated cases suggests a role of SP in the progression and development of tumor. Expression of SP in the current study increased as the proliferation of cells increased. Prevalence of oral cancer in males may be due to the fact that they smoke and use pan, chewing gum, beetle nut etc. in this region. SP antagonists can help in the reduction and inhibition of oral cancer. SP has a diagnostic value with sensitivity of 92.5% and specificity of 93.7%. The positive predictive value is 96.2% and the negative predictive value 88.2%.
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http://dx.doi.org/10.1016/j.prp.2014.09.016DOI Listing
March 2015

Hospital-based study of epithelial malignancies of endometrial cancer frequency in lahore, pakistan, and common diagnostic pitfalls.

Patholog Res Int 2014 6;2014:179384. Epub 2014 Jan 6.

Fatima Memorial College of Medicine and Dentistry, Lahore 54000, Pakistan.

The current study was conducted to see the frequency of epithelial malignancies of endometrium with focus on the common diagnostic pitfalls and identify morphological and immunohistochemical markers helpful in the differential diagnosis between different subtypes. It is a retrospective descriptive study carried out on 52 specimens of endometrial tumors received in Fatima Memorial Hospital, Lahore, Pakistan, during three years (2010-2012). Patients were divided into 5 age groups: <40, 41-50, 51-60, 61-70, and >70 yrs. Tissues were fixed in 10% formalin and processed and stained with haematoxylin-eosin. Stained slides were examined to determine the histological types by WHO classification, and immunohistochemistry for WT1, p53, ER/PR, and MIB1 was done in cases where morphology alone was not helpful in making a confirmed diagnosis. 80% of specimens were of endometrioid adenocarcinomas, 11% of serous tumors, 4% of clear cell carcinoma, and 4% of squamous cell carcinomas involving both cervix and endometrium. Most of the patients (28.84%) with endometrial carcinomas fall in the age range of 51-60 yrs. Endometrioid adenocarcinoma is the most common type of epithelial endometrial malignancies. Morphology is the keystone in the evaluation of these tumors, but immunohistochemistry can also be helpful in establishing the correct diagnosis.
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http://dx.doi.org/10.1155/2014/179384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913386PMC
February 2014

Genetic analysis of prolactin gene in Pakistani cattle.

Mol Biol Rep 2013 Oct 25;40(10):5685-9. Epub 2013 Sep 25.

Department of Pathology/Molecular Cell Biology, King Edward Medical University, Lahore, Pakistan.

Prolactin (PRL) is a polypeptide hormone, secreted mainly by the anterior pituitary gland. It is involved in many endocrine activities. The key functions of PRL are related to reproduction and lactation in mammals. To ascertain the presence of polymorphisms in the bovine PRL gene (bPRL), the bPRL gene was sequenced. Five mutations were identified in exonic region and eleven in associated intronic regions in 100 cattle from four Pakistani cattle breeds. Haplotype of predicted amino acid changes represent a common alteration at codon 222 from R-Arginine into K-Lysine in all four breeds. Significant statistical variations were observed in the distribution of single nucleotide polymorphism (SNP) in various cattle populations. However, on basis of present study, an association of these SNPs with milk performance traits in four Pakistani cow breeds cannot be truly replicated but at least can be effective DNA markers for some of the breeds studied. Linkage analysis between these SNPs on larger populations can be useful for the association with milk production traits. Furthermore, present study may be used for marker-assisted selection and management in cattle breeding program in local cattle breeds.
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http://dx.doi.org/10.1007/s11033-013-2670-8DOI Listing
October 2013

Developmental alterations of the spinal trigeminal nucleus disclosed by substance P immunohistochemistry in fetal and infant sudden unexplained deaths.

Neuropathology 2011 Aug 30;31(4):405-13. Epub 2011 Jan 30.

Lino Rossi Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS, Department of Surgical, Reconstructive and Diagnostic Sciences, University of Milan, Milan, Italy.

We investigated the immunohistochemical expression of substance P (SP) in the brainstems of 56 subjects aged from 17 gestational weeks to 10 post natal months, who died of unknown (sudden unexplained fetal deaths and SIDS) and known causes (controls). The goals of this study were: (i) to obtain basic information about the expression of SP during the first phases of human nervous system development; (ii) to evaluate whether there are alterations of this neuromodulator in victims of sudden death; and (iii) to verify any correlation with maternal cigarette smoking. Immunohistochemistry demonstrated SP immunoreactivity in the caudal trigeminal nucleus area, with a progressive increase in the density of SP-positive fibers of the corresponding tract during normal development from fetal life to the first post natal months. Delineation of the structure of the human trigeminal nucleus, little investigated so far, provided essential data on its morphologic and functional development. Instead, a negative or low SP expression was detectable in the fibers of this tract in a wide subset of SIDS victims and, conversely, a high SP-expression in a wide subset of sudden fetal deaths. We postulate, on the basis of these results, that SP has a functional importance in the early phases of central nervous system development and in the regulation of autonomic functions. In addition, the observation of a significant correlation between sudden unexplained death, altered SP staining and maternal smoking leads us to suggest a close relation between the absorption of cigarette smoke in utero and a decreased functional activity of the trigeminal nucleus, that can trigger sudden death of the fetus during pregnancy or of the infant in the first months of life.
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http://dx.doi.org/10.1111/j.1440-1789.2010.01190.xDOI Listing
August 2011

Neuropathology of the intermediolateral nucleus of the spinal cord in sudden unexplained perinatal and infant death.

Int J Dev Neurosci 2010 Apr 18;28(2):133-8. Epub 2010 Jan 18.

Lino Rossi Research Center for The Study and Prevention of Unexpected Perinatal Death and SIDS-Department of Surgical, Reconstructive and Diagnostic Sciences, University of Milan, Via della Commenda, 19, Milan 20122, Italy.

Experimental studies have demonstrated that breathing activity in rats is generated early in embryonic stages in rostral spinal cord, precisely in the intermediolateral nucleus, then establishing a spinal cord-brainstem network. In this study we aimed to individuate and to define the developmental steps of the intermediolateral nucleus, still inadequately known in humans, in the thoracic spinal cord of a large series of perinatal and infant death victims, aged from 17 gestational weeks to 10 months of life. Besides we investigated a possible link between alterations of this nucleus and sudden unexplained perinatal and infant death. The normal developmental pattern of the human intermediolateral nucleus consists of a progressive maturation of its neurons, that change from a round to a polygonal shape with long axons and significantly decrease in number. Various degrees of intermediolateral nucleus hypodevelopment (neuronal immaturity in a normal structure/hypoplasia/agenesis) were found almost exclusively in unexplained fetal and infant death victims. Besides, a significant correlation was found between maternal smoking in pregnancy and the neuropathological results. In conclusion this work underlines the negative effects of prenatal nicotine exposure on the development of autonomic nervous centers checking the vital functions, already in early gestational stages, when the integrity of the intermediolateral nucleus is indispensable for the first breathing bursts.
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http://dx.doi.org/10.1016/j.ijdevneu.2010.01.001DOI Listing
April 2010
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