Basic Medical Sciences Institute Research Articles

Editorial Comment: Hyperlipidaemia and cardiovascular disease and impact of early cholesterol accumulation.

aDepartment of Endocrinology, Morbid Obesity, and Preventive Medicine, Norwegian National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital bDepartment of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo cDepartment of Medical Genetics, Unit for Cardiac and Cardiovascular Genetics, Oslo University Hospital, Oslo, Norway Correspondence to Kirsten B. Holven, PhD, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, PO Box 1046 Blindern, 0316 Oslo, Norway. Tel: +47 22 85 13 61; e-mail: [email protected]

Clinical Efficacy and Safety of Tacrolimus in Pakistani Living Donor Liver Transplant Recipients.

To evaluate the association between tacrolimus trough levels and dosage in Pakistani patients undergoing live donor liver transplantation (LDLT), and the efficacy and adverse effects at different tacrolimus trough levels and dosages. An observational study. Shifa International Hospital, Shifa Tameer-e-Millat University, Islamabad and Basic Medical Sciences Institute, Karachi, from September 2016 to October 2018. Sixty liver transplant recipients were included. Demographics, clinical data, tacrolimus trough levels and doses were monitored as per routine protocol. Electrochemiluminescence immunoassay (ECLIA) was used to measure tacrolimus trough levels. Acute cellular rejection (ACR), sepsis and other adverse events were monitored at different tacrolimus trough levels in early post-transplantation period. Mean age of transplant recipients was 49.1 ± 10.6 years. Mean tacrolimus trough levels were 6.1 ± 2.2 ng/ml and mean dose was 0.94 ± 0.3 mg. Sepsis (27%) psychosis (20%), seizures (10%), and renal insufficiency (13%) were the most common adverse effects. Acute cellular rejection (ACR) was observed in 15% patients. Patients with sepsis had significantly high mean tacrolimus levels of 7.7 ± 2.5 ng/ml versus 5.5 ± 1.9 ng/ml (p=0.001). Mean tacrolimus trough levels in patients with ACR were significantly lower (4.05 ± 1.6 ng/ml vs. 6.43 ± 2.2ng/ml, p=0.003). None of the patients with a single tacrolimus trough level >10 ng/ml experienced ACR. A tacrolimus trough level between 5 to 7.5 ng/ml appears to be safe in Pakistani liver transplant recipients significantly minimising the risk of ACR and other adverse events.

Spectrum of Tp53 gene mutation in basal cell carcinoma and its morphological subtypes in people of color.

Objectives: Basal cell carcinoma (BCC) is the most common cutaneous malignancy in white population. The pattern of exon specific p53 mutations in BCC and its subtypes remain undetected in our population. This study was designed to evaluate the prevalence and mutational spectrum of p53 mutations in basal cell carcinoma (BCC) and its subtypes in people of color in the population of Karachi, Pakistan. Study Design: Retrospective cross sectional study. Setting: Department of Pathology, Basic Medical Sciences Institute, Jinnah Post Graduate Medical Center Karachi, Pakistan. Period: Five-year study from January 2012 to December 2016. Material and Methods: Convenient sampling technique was used. Sample size was calculated using open EPI software. Analysis of 32 BCC cases for p53 gene mutations in exons 5-8 was detected by polymerase chain reaction technique. Sebaceous carcinoma and malignant melanoma were used as positive controls and normal skin was used as negative control. Results: Out of 32 BCC cases, 26 (81.2%) displayed p53 exon mutations. The number of cases with single exon mutation was 17 (65.3%). Exon 5 mutation was most frequently observed in 8 (30.7%) cases. This was followed by 5 (19.2%) cases with exon 6 mutation and 4 (15.3%) cases with exon 8 mutation. None of the cases revealed exon 7 mutation. A considerable number 9 (34.6%) of BCC displayed dual exon mutation. Dual mutations of exon 6 & 8 were seen in 6 (23%) cases. Exon 5 & 7 mutation was noted in 2 (7.6%) cases followed by a single (3.8%) case with exon 6&7 mutation. The highest number 12 (46.1%) of single and dual exon mutations was recorded in nodular subtype of BCC. Conclusion: The current study confirms the expression of p53 gene mutation in BCC in colored population. Majority of the single mutations were observed in exon 5. Dual exon mutation was the most notable finding of this study. The highest number of single and dual exon mutations was recorded in nodular form of BCC.

Frequency and morphological study of testicular germ cell tumor.

Objectives: To assess the frequency of various histopathological types of testicular germ cell tumor in our study population. The prime identification of testicular germ cell tumor is important to prevent the advance stage of cancers. The present study was design to assess the frequency of different morphological types of testicular germ cell tumor which have a mirror effect on the treatment and prognosis of tumor. Study Design: Cross sectional study. Setting: Department of pathology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre Karachi. Period: 10 years period from 1st January 2006 to 31st December 2015. Material and Methods: A 34 cases of testicular germ cell tumor were studied for morphological features using all properly formalin fixed, paraffin embedded surgical pathological testicular specimens received during the above period. All relevant clinical information was recorded on designed proformas. Section were taken and stained with hematoxylin and eosin. Data entered and analysed through computer software SPSS version 21. Results: The result of study showed that the frequency of testicular germ cell tumor was 0.80% among all malignancy in male. Out of 36 cases of testicular tumor, 34 (94.5%) were germ cell tumors and remaining 02 (5.5%) cases were sex cord stromal tumor. Among 34 cases of germ cell tumor 12 (35.2%) cases of mixed germ cell tumor found which was the most common between them, followed by seminoma 10 (29.4%) cases. However 05(14.7%) of yolk sac tumor, 04 (11.6%) of teratoma and 03(8.8%) of embryonal tumor were found. Conclusion: Results revealed that frequency of different types of testicular germ cell tumor in this study were in accordance to national and international studies. However the incidence of tumor varies noticeably in different geographical areas. Different pattern of seminomas and non – seminomas also may be emerging.

PREVALENCE OF CARBAPENEM-RESISTANT ACINETOBACTER BAUMANNII (CRAB) IN MEDICAL AND SURGICAL INTENSIVE CARE UNITS (ICUS) OF JPMC, KARACHI

Background: Antimicrobial resistance is one of the research priorities of health organizations due to increased risk of morbidity and mortality. Outbreaks of nosocomial infections caused by carbapenem-resistant Acinetobacter Baumannii (CRAB) strains are at rise worldwide. Antimicrobial resistance to carbapenems reduces clinical therapeutic choices and frequently led to treatment failure. The aim of our study was to determine the prevalence of carbapenem resistance in A. baumannii isolated from patients in intensive care units (ICUs). Methods: This cross-sectional study was carried out in the Department of Microbiology, Basic Medical Sciences Institute (BMSI), Jinnah Postgraduate Medical Centre (JPMC), Karachi, from December 2016 to November 2017. Total 63 non-repetitive A. baumannii were collected from the patients’ specimens, admitted to medical and surgical ICUs and wards of JPMC, Karachi. The bacterial isolates were processed according to standard microbiological procedures to observe for carbapenem resistance. SPSS 21 was used for data analysis. Results: Out of the 63 patients, 40 (63.5%) were male. The age of the patient ranged from 15-85 year, with average of 43 year. 34.9% patients had been hospitalized for 3 days. Chronic obstructive pulmonary disease was present in highest number with average of 58.7% for morbidity. Number of patients on mechanical ventilation was highest (65.1%). All isolates were susceptible to colistin. The resistance to ampicillin-sulbactam, ceftazidime, ciprofloxacin, amikacin, piperacillin- tazobactam and meropenem was 82.5%, 81%, 100%, 87.3%, 82.5% and 82% respectively. Out of 82% CRAB, 77% were obtained from ICUs. Conclusion: This study has revealed the high rate of carbapenem resistance in A. baumannii isolates in ICUs thus leaving behind limited therapeutic options.

Remarkable effect of topical betamethasone valerate 0.1% on progress of psoriasis disease.

Introduction: Psoriasis is immuno-inflammatory condition devouring huge negative impact on patient’s life as compare to other diseases. Topical regimen is the standard treatment for mild to moderate psoriasis disease. The data of effectiveness of Betamethasone Valerate 0.1% on large number of psoriatic patients were being deficient in. Objectives: This study evaluates the Topical Betamethasone Valerate 0.1%impact on patient’s life in relation to efficacy and safety. Design: Interventional experimental study. Setting: Study was carried out Basic medical sciences institute (BMSI) alliance with Dermatology Department JPMC, Karachi. Period: June 2013 to June 2016. Methods: 75 chronic plaque type psoriatic patients prescribed Betamethasone Valerate (0.1%) topically along with placebo for 6 months once daily (one week interval after every three week application). The therapeutic effectiveness and safety of studied drug were assessed by means of PASI, DLQI and hsCRP. The results analyzed by using repeated ANOVA. Results: Results revealed that as compare to baseline all parameters were significantly reduced with mean percentage change were 75.001±0.0563, 72.215±3.17and 33.692±7.980 for PASI, DLQI and hsCRP respectively at the end of study. Safety profile of therapy showed non-significant outcomes. Conclusion: Betamethasone valerate 0.1% is better treatment option in mild to moderate psoriatic patients to improve quality of life and decrease disease severity.

Assessment and impact of a biosecurity course in raising the awareness of students at the Jinnah post graduate Medical Center, Pakistan

IntroductionPakistan Biological Safety Association (PBSA) is a not for profit, nongovernmental, professional organization established in 2008 and is striving to promote and implement Bio risk management in Pakistan. PBSA accelerated its program for strategic training of the national life scientists from 2013 and is still working on that mandate with the help of Fogarty International Center (FIC) & National Institute of Health USA and other international organizations working on this Global Health Security Initiative and subsequently Agenda (GHSA) Aims & ObjectivesThis biosafety training program was developed for capacity building of M.Phil. and PhD graduates the future laboratory users of Basic Medical Sciences Institute (BMSI), Jinnah Post Graduate Medical Center which is the largest tertiary care hospital in Karachi, Pakistan involved in Research &Development (R&D) in medical sciences. Materials & MethodsThis Pre post study was carried at Basic Medical Sciences Institute (JPMC), during the period of October 2018 to January 2019. A total of 48 (16 PhD. 32 M.Phil.) Grads students participated in the following study. The training program is administered through, custom made 4-month course having 16 contact hours also 4 hours of practical training. Training was evaluated using written assessment. The pre and post-training test was conducted after each session. Each test comprised of 15 multiple choice questions (MCQs) pre and post session making it 30 MCQs in total for each session. A final assessment consisting 30 MCQs conducted at the end of course. ResultsThere was vast difference observed in the post assessment results as compared to the pre assessment results. At the end of the course final assessment was carried out which gave an overall impression of vast change (83.3%) in awareness regarding bio risk management among the graduate students, which reflected the efficacy of this training. To ensure the validity of results and the intention to improvise the quality of course in future, feedback regarding the course and trainer was obtain through Likert scale. Reliability of Likert scale carried through Cronbach’s alpha, showed all variables with a maximum score of 0.9, indicating high reliability of the generated feedback evaluation. ConclusionThis study highlighted that through concerted efforts of professional organizations, proper awareness of public and concerned personals, regarding Biosafety & Biosecurity can certainly reduce the chances of errors and will ensure potential safety and security to the laboratory workers, community and environment, potentially exposed to these pathogens & toxins which are regarded as biohazards.

Hepatitis C virus genotype 3a: Predictive factors associated with treatment response in patients of Peshawar.

Hepatitis C Virus (HCV) is a flavivirus responsible for causing chronic liver diseases including cirrhosis and hepatocellular carcinoma. Identification of various patient and virus-related factors that can help predict response to antiviral therapy is extremely important in formulating the best therapeutic strategy for each patient either to continue or stop the therapy. The present study aimed to determine Sustained Virological Response (SVR) in HCV genotype 3a infected patients that received combination therapy of Sofosbuvir and Ribavirin and to investigate various factors that can help predict SVR. Study Design: Longitudinal Study Settings: Institute of basic Medical Sciences, Khyber Medical University, Peshawar (IBMS, KMU). Period: July 2016 to September 2017. Materials and Methods: Treatment response was evaluated among 100 HCV genotype 3a infected patients that received Sofosbuvir and Ribavirin therapy for 24 weeks. Various baseline parameters including hematological, biochemical and viral profiles of were recorded. HCV genotype determination was carried out by type specific nested PCR based genotyping assay. Viral load was determined at baseline, at 12 weeks for Early Virological Response (EVR) and at 24 weeks of treatment for SVR. Viral RNA quantification was carried out by Real Time PCR. Results: Out of 100 patients, SVR was observed in 83% of patients; while 17% of the chronic HCV 3a infected patients were Non-Responders (NR). Mean age of patients was low 34 ± 9.8 among patients who achieved SVR as compared to patients with non-response (41 ± 10). The 24 weeks Alanine aminotransferase (ALT) levels were significantly lower among patients with SVR (p-value ≤ 0.05). Although statistically not significant, baseline viral load was higher in NR group (p-value ≥ 0.05), than those with SVR. Association of EVR with SVR was found statistically significant (OR= 2.8, 95% CI 1.2-6.4, p-value ≤ 0.05). Conclusions: The current study indicated that pre and on-treatment monitoring of patients receiving anti-viral therapy is important for the management of patients with chronic HCV infection.

Ifenprodil and Flavopiridol Identified by Genome-Wide RNAi Screening As Effective Drugs to Ameliorate Murine Acute Lung Injury after Influenza A H5N1 Virus Infection

Background: Due to limits of effective treatments, avian influenza A H5N1 virus is most lethal influenza virus strain that causes severe acute lung injury (ALI). To develop effective drugs ameliorating H5N1-induced ALI, we explore an RNA interference (RNAi) screening method to monitor changes in cell death induced by H5N1 infection. According to estimation of Bernard Munos, a drug-development advocacy organization in Washington DC, the proportion of drugs that in theory could be repositioned is probably approximately 75%. Methods: We screened 19,424 RNAi in A549 lung epithelial cells and examined cell death induced by H5N1 infection. These screenings identified 1137 host genes for which knockdown altered cell viability by over 20%. DrugBank searches of these 1137 host genes identified 146 validated druggable target genes with 372 drug candidates. We obtained 104 commercially available drugs with 65 validated target genes and examined their improvements in cell viability following H5N1 infection. We identified 28 drugs that could significantly recover cell viability following H5N1 infection and tested 10 in an H5N1-induced ALI mouse model. Findings: The neurological drug ifenprodil and anticancer drug flavopiridol markedly decreased infiltrated leukocytes and lung injury scores in infected mouse lungs and significantly ameliorated lung edema in infected mouse lung tissue. Interpretation: Ifenprodil is an antagonist of N-methyl-D-aspartate (NMDA) receptor, which is linked to inflammation and lung injury. Flavopiridol is an inhibitor of CDK4, which is linked to leukocyte migration and lung injury. These results suggest that ifenprodil and flavopiridol are novel remedies against potential H5N1 epidemics in addition to their proven indications. Furthermore, our strategy for identifying repurposable drugs could serve as a general approach for other diseases. Funding Statement: This work was supported by National Natural Science Foundation of China (81788101, 81490531), Ministry of Science and Technology of China (2015CB553406) and CAMS Innovation Fund for Medical Sciences (2017-I2M-1-009). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Animal experiments in this work were approved by Ethics Committee of Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (ACUC-A02-2017-014).

GENETIC ANALYSIS OF FAMILIES HAVING AUTOSOMAL RECESSIVE INTELLECTUAL DISABILITY

Background: Intellectual disability (ID) is a neuro-developmental defect that is manifested by development delay and learning disability. Such defects may be caused due to chromosomal disorders (trisomy 18 or Down syndrome) or single gene mutation. Its worldwide prevalence is estimated to be 1-3%. The genetic etiology of non-syndromic ID is poorly understood. To date, more than 100 loci have been reported to be associated with non-syndromic ID. The objective of this study was to identify the causative genes for three Materials & Methods: This cross-sectional study was conducted in the Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan from March 2014 to August 2015. The inclusion criteria set for the families was consanguineous relation and more than two patients per family (including cousins). All the patients were tested individually in friendly atmosphere using IQ test to scale the ID on the basis of performance. Thereafter, blood samples were taken by aseptic method and DNA was extracted for the purpose of doing genetic analysis. In genetic analysis, exome sequencing was performed to find the pathogenic variants. Subsequently. Sanger sequencing was also done to see the segregation of pathogenic variants.
 Results: Genetic analysis found mutation in AP4B1 in Family 1, in WDR62 in Family 2, while Family 3 was unremarkable. 
 Conclusion: The study involved genetic analysis of three consanguineous families and found mutation in AP4B1 in Family 1, in WDR62 in Family 2, while Family 3 was unremarkable. The present research will help in devising molecular diagnostic technics for pre-marital and pre-conception testing.

GENETIC ANALYSIS OF FAMILIES HAVING AUTOSOMAL RECESSIVE INTELLECTUAL DISABILITY

Background: Intellectual disability (ID) is a neuro-developmental defect that is manifested by development delay and learning disability. Such defects may be caused due to chromosomal disorders (trisomy 18 or Down syndrome) or single gene mutation. Its worldwide prevalence is estimated to be 1-3%. The genetic etiology of non-syndromic ID is poorly understood. To date, more than 100 loci have been reported to be associated with non-syndromic ID. The objective of this study was to identify the causative genes for three Materials & Methods: This cross-sectional study was conducted in the Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan from March 2014 to August 2015. The inclusion criteria set for the families was consanguineous relation and more than two patients per family (including cousins). All the patients were tested individually in friendly atmosphere using IQ test to scale the ID on the basis of performance. Thereafter, blood samples were taken by aseptic method and DNA was extracted for the purpose of doing genetic analysis. In genetic analysis, exome sequencing was performed to find the pathogenic variants. Subsequently. Sanger sequencing was also done to see the segregation of pathogenic variants. Results: Genetic analysis found mutation in AP4B1 in Family 1, in WDR62 in Family 2, while Family 3 was unremarkable. Conclusion: The study involved genetic analysis of three consanguineous families and found mutation in AP4B1 in Family 1, in WDR62 in Family 2, while Family 3 was unremarkable. The present research will help in devising molecular diagnostic technics for pre-marital and pre-conception testing.

Frequency of dyslipidemia in young overweight and obese students (age 10-16 years) in private schools of swat

Objectives: The objective of the current study was to estimate the frequency of pediatric dyslipidemia in overweight and obese students of private schools in Swat. Study Design: Questionnaire based cross-sectional study. Setting: Three private schools of district Swat. Period: 6 months. Method: Study analysis was done in Research laboratories of Biochemistry Department, Institute of Basic medical Sciences (IBMS), Khyber Medical University Peshawar. Well-designed questionnaires were used for screening of 99 out of 1374 students, including both girls and boys. Anthropometric measurements were taken. Blood samples were collected for the analysis of serum lipids using an Automated Cobas Analyzer. SPSS version 20, Student’s t test and Logistic regression method was used for statistical analysis. Results: The prevalence of dyslipidemia was measured to be 42.4%. A significantly direct association was found between the rate of dyslipidemia and BMI. Highly significant P values were found for serum lipids in obese children as compared to overweight children thus showing strong association between the biochemical Parameters and BMI. Even though rate of dyslipidemia was measured to be a little higher in boys as compared to girls, no statistically significant gender differences were found in serum lipid levels. Conclusion: Reduce long-term complications in adulthood is possible through controlling the serum lipid levels of children and adolescents.

SYPHILIS;

Objectives: To assess serum Neopterin levels in blood donors of local population and to study its relationship with transfusion transmitted infections (TTIs) including syphilis. Study Design: Descriptive cross-sectional study. Place and Duration of Study: This study was carried out in the Department of Physiology LNMC in collaboration with Basic Medical Sciences Institute, (BMSI), and Jinnah Post Graduate Medical Centre (J.P.M.C.) Karachi, from Jan to July 2015.”Methods: Total 174 blood donors were included in the study through random sampling technique. They were screen through the standard procedures used for screening at the JPMC blood bank for WHO recommended diseases. Neopterin was estimated using ELISA. Data analysis was performed using SPSS version 21. Chi square and ANOVA were applied at a confidence level of 95%.”Results: Neopterin level in the sera of syphilis positive blood donors was 5.86 ± 0.78 nmol/l which was within normal range below the cutoff value of 10 nmol/l. Neopterin content in the serum of blood donors who were negative for transfusion transmitted infections was 6.23± 2.19 nmol/l as compared to blood donors testing positive for transfusion transmitted viral infections showing high Neopterin level of 15.10 ± 4.93 nmol/l. (P value 0.001).”Conclusion: Neopterin levels were found to be within normal limits in blood donors testing positive for syphilis However in blood donors with transfusion transmitted viral infections serum neopterin levels were elevated.

Investigation of the Plasma Metabolic and Lipidomic Characteristics of a Chinese Population and Its Application in Biomarker Discovery for Renal Cell Carcinoma

Plasma metabolomics and lipidomics have been commonly used for biomarker discovery for the rich metabolic information they provide. Studies in white and Japanese populations suggested that gender and age can affect circulating plasma metabolite profiles; however, the Chinese population has not been surveyed. In our study, we profiled Chinese plasma metabolome and lipidome in a cohort of 534 healthy adults and reported an overview of metabolic characteristics in the Chinese population. Inter-individual analysis showed that inter-individual variations of the plasma metabolome and lipidome were 0.645 and 0.568, respectively. Further differential analysis indicated that gender and age would affect the metabolic status. Metabolic pathways such as fatty-acid metabolism, nicotinate and nicotinamide metabolism, steroidogenesis process and tryptophan metabolism were found to vary with gender and age. Comparison of metabolism characteristics between Chinese and other western population suggested that plasma metabolomics could reflect regional and ethnic differences, to some extent. Further, using the above strategy, renal cell carcinoma (RCC) biomarkers were explored based on age- and gender-matched healthy subjects, 34 patients with benign kidney lesions and 143 patients with RCC. Metabolic and lipid profiling of the plasma could significantly differentiate cancer cases from healthy controls and benign controls, with an area under the curve (AUC) of 0.971 and 0.839, respectively. Our study provides an overview of plasma metabolic characteristics in a Chinese population and suggests that plasma metabolomics and lipidomics are useful strategies for biomarker discovery. Funding Statement: This work was supported by National Basic Research Program of China (Nos. 2013CB530805 and 2014CBA02005), Major collaborative innovation projects (No. 2017-I2M-1-009), Key Basic Research Program of the Ministry of Science and Technology of China (No. 2013FY114100), the National Natural Science Foundation of China (No. 30970650, 31200614, 31400669, 81371515 and 81670611), Beijing Natural Science Foundation (No. 5132028), Basic scientific research (2017PT310004) and Biologic Medicine Information Center, National Scientific Data Sharing Platform for Population and Health. Declaration of Interests: The authors declare no conflict of interests. Ethics Approval Statement: This study was approved by the Institutional Review Board of the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences.

Clinical efficacy and tolerability of Gabapentinoids with current prescription patterns in patients with Neuropathic pain.

Objective:To investigate the current dosing regimens of gabapentinoids in Pakistani patients with neuropathic pain and to compare their clinical efficacy and tolerability in terms of pain relief and adverse effects using difference in pain score as a treatment outcome.Methods:This observational, prospective study was conducted in 320 patients with neuropathic pain from August 2016 to March 2018 at Basic Medical Sciences Institute (BMSI), Karachi in collaboration with Shifa International Hospital and Benazir Bhutto Hospital, Islamabad. Demographic data, treatment-related adverse effects and pain intensity was documented at recruitment and follow up visits at two, four and eight weeks. Discontinuation due to adverse effects and lack of efficacy were also recorded. Data was entered and analyzed using SPSS version 22.Results:Mean age of patients was 52.57±12.47 and the most common ethnicity were Punjabi speaking population (66%). Diabetic neuropathy (51%) was the most common etiology followed by radicular pain (25%). Mean dosages of pregabalin and gabapentin were 114mg and 470mg respectively. Mean pain score was significantly reduced by gabapentinoids (<0.001). Dizziness, drowsiness and somnolence were frequent adverse effects. Common dosages for pregabalin and gabapentin were 75 mg/day and 300 mg/day respectively.Conclusion:Current dosing regimens of gabapentinoids in Pakistani patients with neuropathic pain were found to be efficacious at low dosages in comparison to international recommended dosages. Gabapentin and pregabalin were both similar in terms of reducing pain score but onset of pain relief was relatively faster with pregabalin. Dizziness, drowsiness and somnolence were frequently reported with both gabapentinoids; however, visual blurring, ataxia and weight gain were observed only with the use of pregabalin. Adverse effects are frequently observed with gabapentinoids which necessitates reverting back to low dosages or switching to other drugs for pain relief.

Expression analysis of cyclooxygenase-2 in patients suffering from esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the aggressive malignancies and mechanisms underlying its pathogenesis remain unclear. Cyclooxygenase-2 (COX-2) enzyme system plays a crucial role in many gastrointestinal malignancies and is an important regulator of cell growth, proliferation, apoptosis, differentiation and transformation. More precise outcome of COX-2 in ESCC is less investigated. In this study we investigated the risk factors of ESCC and expression of COX-2 in Carcinoma in situ (CIS) and ESCC compared to normal esophageal mucosa. ESCC relationship to clinico-pathological parameters using immunohistochemistry was also part of this investigation. Current study was conducted in the Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan. A total of 69 diagnosed patients of ESCC, both Pakistanis and Afghans were enrolled. Various risk factors associated with ESCC were recorded. Mean age at the time of diagnosis was 55 years. Out of 69 patients of ESCC 46 (67%) were users of dipping tobacco (Naswar). Expression of COX-2 was determined in normal esophageal mucosa, CIS and invasive ESCC using Immunohistochemistry (IHC). Differences of mean were computed using ANOVA followed by applying Post Hoc test. Patients were categorized as positive with high expression or negative with low to nil expression. ANOVA showed large differences in expression of COX-2 in normal healthy mucosa compared with CIS and ESCC with the mean difference of -9.529 and -7.370 respectively, p-value being <.05 at 95% confidence interval (CI). No significant difference was noticed in the expression of COX-2 in CIS compared with ESCC with p-value >.05 at 95% CI. Our complete cohort (23–85 years) showed statistically significant difference in the expression of COX-2 gene in ESCC and CIS tissue samples compared with normal healthy mucosa. Results of this study indicate that over-expression of COX-2 is positively associated with ESCC.

Confidence to go the way science takes you.

Anne Simonsen is a Professor at the Department of Molecular Medicine at the Institute of Basic Medical Sciences of the University of Oslo, Norway. Her work focuses on lipid-binding proteins in membrane trafficking and autophagy, and their links to disease.

ASCORBIC ACID

Objectives: To demonstrate the volume changes that are produced byanthracycline Doxorubicin DOX on the testes of mice and designed to study volumetric changesin DOX affected testes with co-administration of antioxidant Vitamin C. Design: An experimentalstudy. Setting: Institute of Basic Medical Sciences. Dow University of Health Sciences. Period:September 2011 to May 2012. Methods: Experimental study using thirty male mice of fiveweeks old were separated into 3 groups (A, B &amp; C). Each group had ten mice and was treatedwith normal saline 1 ml intraperitoneal (IP) in group A, DOX alone (0.003 mg in 0.03ml /gmbody weight IP for 3 doses on 6th, 8th and 10th day of study) in group B and DOX (0.003 mgin 0.03ml /gm body weight IP for 3 doses on 6th, 8th and 10th day of study) + Vitamin C (0.5mg in 0.01ml/gm body weight per orumdaily) in group C. After completion of study, animalswere sacrificed and the testes were kept in Bouin’s fluid and volume was measured. Results:By using SPSSS version 16, statistical analysis was done, using ANOVA test to evaluate thesignificance of concerned parameter among different groups studied. The administration ofDOX induced significant reduction (P &lt;0.001) of volume of testes when compared to controls.However co-administration of Vitamin C with DOX significantly increase (P &lt;0.001) the volumeas compared to DOX group. Conclusion: This study suggested that the antioxidant VitaminC has a significant role in ameliorating the damage of testes induced by DOX, showingimprovement in the morphology and morphometry of testes.

Association rules analysis of Fufang Kushen injection in combination with modern medications in treating lung cancer: real-world study based on hospital information

The present study was aimed to analyze the association rules of Fufang Kushen injection in combination with other modern medications in treating lung cancer based on the electrical medical records in real world clinical situations extracted from hospital information system in Institute of Basic Medical Sciences, China Academy of Chinese Medical Sciences, and provide reference for improving rationality of clinical drug use and exploring the prescription rules as well as subsequent in-depth analysis. The electrical medical records of the hospitalized patients using Fufang Kushen injection for lung cancer were extracted to analyze the frequency distribution characteristics in combined application with western medicine, and Apriori algorithm was used to analyze the specific association rules in combined drug use. A total of 49 597 patients were included in the study. The commonly combined modern medications included 5-HT receptor blockers, antibiotics, chemotherapy drugs, antitumor immune regulating drugs, glucocorticoid drugs and analgesics, which was usually applied in combination with traditional Chinese medications such as those for removing blood stasis, spleen and stomach nourishing drugs, Qi-regulating agent, heat-clearing and detoxifying prescriptions, laxative and Qi invigorating agent in clinical treatment. The results revealed that the distribution characteristics in combined application and association combinations of Fufang Kushen injection had specific rules, consistent with the clinical orientation of this drug in treatment of lung cancer. Such results may provide reference for reasonable application of Fufang Kushen injection in clinical treatment.

CITRULLUS COLOCYNTHIS

Objectives: To evaluate the methanolic extract of Citrullus colocynthis andits different fractions for possible spasmogenic effects on rat’s ileum model. Study Design:An experimental study. Setting: Department of Pharmacology, Institute of Basic MedicalSciences, Khyber Medical University, Hayatabad, Peshawar. Period: August 2016 to March2017. Methodology: Different fractions i.e n-hexane, chloroform, Ethyl acetate, n-butanol andaqueous fractions of methanolic extract were tried in concentrations of 0.01, 0.03, 0.1, 0.3, 1.0,3.0, 5.0, 10 and 15 mg/ml to identify the portion with maximum spasmogens. Results: Aqueousand n-Butanol fractions showed spasmogenic effects on the spontaneous contractions of rat’sileal preparations at the concentrations of 0.1, 0.3, 1.0, 3.0 and 5.0 mg/ml while at 10 and15 mg/ml, they showed spasmolytic effects. Ethyl acetate and chloroform fractions did notshow significant spasmogenic effects, rather showed spasmolytic effects in rabbit’s jejunalpreparations with respective EC50 values of 0.1283 ± 0.007 mg/ml and 2.703 ± 0.235 mg/ml. Respective EC50 values for spasmolytic effects of Ethyl acetate and chloroform fractionsupon KCl induced contractions were 5.37 ± 0.515 mg/ml and 12.36 ± 1.484 mg/ml. RespectiveEC50 (log [Ca++] M) of ethyl acetate fraction at 1mg/ml vs control were -2.563 ± 0.04 and-2.846 ± 0.035. Similarly, respective EC50 (Log[Ca++]M) in the absence and presence of0.1 μM verapamil were -2.45 ± 0.06 and -1.7 ± 0.07. EC50 (log [Ca++] M) for control vschloroform fraction at 3 mg/ml and 5 mg/ml were -2.95 ± 0.035 vs -3.02 ± 0.03 and -3.06 ±0.0264, respectively. Similarly, respective EC50 (Log[Ca++]M) in the absence and presenceof 0.1 μM verapamil were -2.45 ± 0.06 and -1.7 ± 0.07. Conclusion: Thus, it is concluded thatspasmogens concentrated in the residual aqueous fraction followed by n-butanol fraction whilespasmolytic constituents are concentrated in the ethyl acetate fraction followed by chloroformfraction.