Unscrewing the DHT-Blocking Properties of Allium cepa Extract: Virtual Screening of Active Compounds Against 5-Alpha Reductase and Evaluation of ADME/T Properties of Compounds

Androgenetic alopecia (AGA) occurs in genetically prone men and women and is defined by pattern-related, non-scarring hair follicle shrinkage. It is estimated that up to 80% of men and 50% of women will be affected by AGA at some stage in their lives. The underlying pathophysiology may be traced back to the enzyme 5-alpha-reductase, which is responsible for the conversion of testosterone to dihydrotestosterone (DHT), a more powerful androgen, and its accumulation in hair follicles leads to hair loss. The therapeutic approach for treating AGA mainly relies on the inhibition of 5-alpha- reductase. Allium cepa (onion) extract is in trend as a natural remedy for the treatment of AGA. The study aims at in-silico and ADME/T analysis of active compounds present in onion extract against 5-alpha-reductase to evaluate and visualize protein-ligand interaction.

Ghost ileostomy release down: our initial experience

Background: Many publications describe the advantages of the creation of ghost ileostomy (GI) to prevent the need for formal covering ileostomy in more than 80% of carcinoma rectum patients. However, none of the papers describes exactly how to ultimately remove the GI in these 80% of patients in whom it doesn't need formal maturation. Aim: To describe and evaluate the ghost ileostomy release down (GIRD) technique in terms of feasibility, complications, hospital stay, procedure time etc. in patients with low anterior resection/ultra-low anterior resection (LAR/uLAR) with GI for carcinoma rectum. Method: The present was a prospective cohort study of patients with restorative colorectal resections with GI for carcinoma rectum, Postoperatively the patients were studied with respect to ease and feasibility of the release down of GI and its complications. The data was collected, analyzed and inference drawn. Results: A total of 26 patients needed the GIRD and were included in the final statistical analysis of the study. The procedure was done between 7th to 16th postoperative days (POD) and was successful in all patients without the need of any additional surgical procedure. None of the patients required any local anesthetic injection or any extra analgesics. The average time taken for procedure was 5-minutes and none of the patients had any significant difficulty in GI release. There were no immediate postprocedure complications. Conclusion: The GIRD technique is a simple, safe, and quick procedure done around the 10th POD that can easily be performed by the bedside of patient without the need of any anesthesia or additional analgesics. (AU)

Comparative study of atienuation of needle prick pain of spinal anaesthesia by local infiltration analgesia versus EMLA skin patch

Introduction: Needle prick pain is a distressing event for a pa?ent receiving spinal anaesthesia. A ‘Needle piercing the spine’ might be physically and mentally trauma?zing for many pa?ents. This may lead to unwanted panic and anxiety during the procedure of spinal anaesthesia. To avoid this distressing needle prick pain, many clinicians have resorted to the prac?ce of giving injec?ons of local anaesthe?c or local applica?on of EMLA cream or patch at the site of spinal puncture beforehand for anaesthe?zing the skin and subcutaneous ?ssues. Methods: A prospec?ve cohort study was done. Those enrolled pa?ents were assessed by an expert anesthesiologist, who was not part of the research team, and he prescribed pa?ents either EMLA cream or regular standard lignocaine infiltra?on anaesthesia and labelled them as Group E and Group L respec?vely. The pain score was assessed using a Visual Analogue Scale. Result: A total of 64 pa?ents were enrolled in the study33 in Group E and 31 in Group L. Both groups had an almost similar number of pa?ents who had a similar extent of surgery. Univariate analysis showed that the mean pain score (VAS) was significantly higher in Group E pa?ents compared to that in Group L, p<0.001. The mul?variate analysis had similar findings a?er controlling confounding factors in mul?ple regression analysis. Conclusion: Local 2% lignocaine injec?on achieved significantly more pain reduc?on during spinal needle inser?on compared to the applica?on of an EMLA patch before spinal anaesthesia.

Clinical and Safety Outcomes of Endovascular Therapy 6 to 24 Hours After Large Vessel Occlusion Ischemic Stroke With Tandem Lesions / 대한뇌졸중학회지

Background@#and Purpose Effect of endovascular therapy (EVT) in acute large vessel occlusion (LVO) patients with tandem lesions (TLs) within 6–24 hours after last known well (LKW) remains unclear. We evaluated the clinical and safety outcomes among TL-LVO patients treated within 6–24 hours. @*Methods@#This multicenter cohort was divided into two groups, based on LKW to puncture time: early window (<6 hours), and late window (6–24 hours). Primary clinical and safety outcomes were 90-day functional independence measured by the modified Rankin Scale (mRS: 0–2) and symptomatic intracranial hemorrhage (sICH). Secondary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction score ≥2b), first-pass effect, early neurological improvement, ordinal mRS, and in-hospital and 90-day mortality. @*Results@#Of 579 patients (median age 68, 32.1% females), 268 (46.3%) were treated in the late window and 311 (53.7%) in the early window. Late window group had lower median National Institutes of Health Stroke Scale score at admission, Alberta Stroke Program Early Computed Tomography Score, rates of intravenous thrombolysis, and higher rates for perfusion imaging. After adjusting for confounders, the odds of 90-day mRS 0–2 (47.7% vs. 45.0%, adjusted odds ratio [aOR] 0.71, 95% confidence interval [CI] 0.49–1.02), favorable shift in mRS (aOR 0.88, 95% CI 0.44–1.76), and sICH (3.7% vs. 5.2%, aOR 0.56, 95% CI 0.20–1.56) were similar in both groups. There was no difference in secondary outcomes. Increased time from LKW to puncture did not predicted the probability of 90-day mRS 0–2 (aOR 0.99, 95% CI 0.96–1.01, for each hour delay) among patients presenting <24 hours. @*Conclusion@#EVT for acute TL-LVO treated within 6–24 hours after LKW was associated with similar rates of clinical and safety outcomes, compared to patients treated within 6 hours.

Tissue Clock Beyond Time Clock: Endovascular Thrombectomy for Patients With Large Vessel Occlusion Stroke Beyond 24 Hours / 대한뇌졸중학회지

Background@#and Purpose Randomized trials proved the benefits of mechanical thrombectomy (MT) for select patients with large vessel occlusion (LVO) within 24 hours of last-known-well (LKW). Recent data suggest that LVO patients may benefit from MT beyond 24 hours. This study reports the safety and outcomes of MT beyond 24 hours of LKW compared to standard medical therapy (SMT). @*Methods@#This is a retrospective analysis of LVO patients presented to 11 comprehensive stroke centers in the United States beyond 24 hours from LKW between January 2015 and December 2021. We assessed 90-day outcomes using the modified Rankin Scale (mRS). @*Results@#Of 334 patients presented with LVO beyond 24 hours, 64% received MT and 36% received SMT only. Patients who received MT were older (67±15 vs. 64±15 years, P=0.047) and had a higher baseline National Institutes of Health Stroke Scale (NIHSS; 16±7 vs.10±9, P<0.001). Successful recanalization (modified thrombolysis in cerebral infarction score 2b-3) was achieved in 83%, and 5.6% had symptomatic intracranial hemorrhage compared to 2.5% in the SMT group (P=0.19). MT was associated with mRS 0–2 at 90 days (adjusted odds ratio [aOR] 5.73, P=0.026), less mortality (34% vs. 63%, P<0.001), and better discharge NIHSS (P<0.001) compared to SMT in patients with baseline NIHSS ≥6. This treatment benefit remained after matching both groups. Age (aOR 0.94, P<0.001), baseline NIHSS (aOR 0.91, P=0.017), Alberta Stroke Program Early Computed Tomography (ASPECTS) score ≥8 (aOR 3.06, P=0.041), and collaterals scores (aOR 1.41, P=0.027) were associated with 90-day functional independence. @*Conclusion@#In patients with salvageable brain tissue, MT for LVO beyond 24 hours appears to improve outcomes compared to SMT, especially in patients with severe strokes. Patients’ age, ASPECTS, collaterals, and baseline NIHSS score should be considered before discounting MT merely based on LKW.

Bidirectionality of smoking and depression in adolescents: a systematic review

Abstract Introduction Recently, evidence has been accumulating that both smoking and mental health disorders are continuously increasing among adolescents. This systematic review elucidates the research into evidence of the direction of the association and risk factors influencing the relationship between smoking and depression. We also highlight recent studies on the effects of electronic cigarettes and developments on the association between depression and smoking. Methods A literature search was conducted on databases including PubMed, Ovid Medline, EMBASE, and PsycINFO and in relevant neurology and psychiatry journals. Terms used for electronic searches included smoking, tobacco, cigarettes; depression; adolescent, youth; direction. Relevant information was then utilized to synthesize findings on the association between smoking and depression among adolescent population. Results The initial database searches yielded 2,738 related articles. After screening and cross-referencing, duplicate articles, articles published in languages other than English, and studies on animals, social and lifestyle factors, mood disorders, and substance use were excluded. Of these, a total of 122 publications only focusing on smoking and depression in the adolescent population were selected for synthesis in this qualitative systemic review. These include 110 original research articles, eight meta-analyses and reviews, and four reports and websites. Conclusion The relationship between smoking and depression in the literature does not reflect the cause-effect relationship. The lack of evidence on the direction of the association may reflect futile study designs, confounding factors and/or use of indirect measures of depression and quantification of smoking. Future prospective randomized studies should target elucidation of the causal association.

Surgical Management of Ranula- Floor of Mouth by Marsupialization: A Case Series.

Introduction: The extravasation of saliva from the sublingual gland on the floor of the mouth results in a ranula. The most typical presenta?on is swelling under the tongue. The mylohyoid muscle may allow it to herniate, Causing a plunging ranula. Ranula can be treated in many ways, including ranula excision alone, excision of the sublingual gland with or without ranula, aspira?on of cys?c fluid, sclerotherapy, marsupializa?on, incision and drainage. Material and methods: This case study includes six pa?ents with ranula who underwent surgical treatment by marsupializa?on. The indica?ons, age and sex distribu?on, Marsupializa?on methods, pathology reports, recurrence rates, and complica?ons were seen. Results: Out of 6 pa?ents in our case series, no one pa?ent has shown to be any recurrence or complica?ons of marsupializa?on. Conclusions: Management of Ranula by Marsupializa?on is a good op?on, but if it recurs a?er marsupializa?on, Excision of the lesion and the affected gland is the best course of act?on.

Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality / 대한뇌졸중학회지

Background@#and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. @*Methods@#We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). @*Results@#There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. @*Conclusions@#During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Formulation, Optimization, in vitro and in-vivo evaluation of levofloxacin hemihydrate Floating Tablets

Abstract The objective of the present investigation was to design, optimize and characterize the gastro retentive floating levofloxacin tablets and perform in-vivo evaluation using radiographic imaging. The floating tablets were prepared by using polymers i.e hydroxy propyl methyl cellulose (HPMC-K4M) and carbopol-940 individually and in combination by nonaquous granulation method. All the Formulations were evaluated for swelling index (S.I), floating behavior and in-vitro drug release kinetics. The compatibility study of levofloxacin with other polymers was investigated by FTIR, DSC, TGA and XRD. Results from FTIR and DSC revealed no chemical interaction amongst the formulation components. The optimized formulation (F11) showed floating lag time (FLT), total floating time (TFT) swelling index (S.I) of 60 sec, >16h and approximately 75 %, respectively. Moreover, F11 showed zero order levofloxacin release in simulated gastric fluid over the period of 6 h. X-ray studies showed that total buoyancy time was able to delay the gastric emptying of levofloxacin floating tablets in rabbits for more than 4 hours. In conclusion the optimized formulation (F11) can be used for the sustained delivery of levofloxacin for the treatment of peptic ulcer.

Therapeutic potential and bioactive phenolics of locally grown Pakistani and Chinese varieties of ginger in relation to extraction solvents

Abstract Current study compares the Therapeutic/nutra-pharmaceuticals potential and phenolics profile of Pakistani grown Pakistani and Chinese varieties of ginger. Crude yield of bioactive components from the varieties tested, using different extraction solvents including chloroform, ethyl acetate, ether, methanol, ethanol and distilled water. The crude bioactives varied from 14.1-82.5%. The highest extraction yield was noted for Pakistani species. The HPLC analysis revalued significant amounts of phenolics including vanillin, protocatechuic, vanillic, ferulic, sinapinic and cinnamic acids. The highest anti-inflammatory activity was shown by ethanolic extract of Pakistani variety (IC50: 26.5±1.8) whereas Chinese variety exhibited potent anticancer potential against MCF-7 cell line (Inhibition: 91.38 %). The Chinese variety in general showed higher phenolics and anticancer, while the Pakistani exhibited higher anti-inflammatory activity. Pakistani grown ginger and ethanolic extract of Chinese ginger showed highest antimicrobial activity against Pseudomonas aeruginosa 18.0±0.02 & 15.00±0.02 mm respectively. Minimum results obtained with water for both varieties of ginger with range of 7.2±0.22 and 6±0.07 respectively. Moreover, the phenolics composition, anti-inflammatory, antibacterial and anticancer activities of both tested varieties of ginger were notably affected as a function of extraction solvents. Our findings advocate selection of appropriate solvent for recovery of effective phenolic bioactive compounds from ginger verities to support the Nutra-pharmaceutical formulation.

Role of covering Ileostomy in causation of anastomotic strictures in low anterior resections for rectum carcinoma / O papel da ileostomia de proteção como causa das estenoses anastomóticas nas ressecções anteriores de reto

Abstract Background Colorectal resection anastomosis is the commonest cause of rectal strictures. Anastomotic site ischemia, incomplete doughnuts from stapled anastomosis and pelvic infection, are some of the risk factors that play a role in the development of postoperative rectal strictures. However, the role of diverting stoma in the development of rectal strictures has not been studied extensively. Objectives To study the difference in the occurrence of anastomotic strictures (AS) in patients submitted to low anterior resection (LAR) with covering ileostomy (CI), and to LAR without CI for carcinoma rectum. Methods This was a prospective, comparative case control study carried out at a tertiary care referral center. Low anterior resection with covering ileostomy was performed in patients with rectum carcinoma in the study group, while LAR without covering ileostomy was performed in the control group. The study group had 29 patients, while the control group had 33 patients with rectum carcinoma. Results During themean follow-up period of 9.1months, 8 (28%) patients in the study group and 2 (6%) patients in the control group developed AS (p =0.019). Out of these 8 patients with AS in the study group, 50% had Grade-I AS, 25% had Grade-II AS, while 25% of the patients had Grade-III (severe) AS. However, both patients who developed AS in the control group had a mild type (Grade I) of AS. Conclusion Covering ileostomy increases the chances of AS formation after LAR for rectum carcinoma. Also, the SKIMS Clinical Grading of Rectal Strictures is a simple and

Resumo Introdução A anastomose de ressecção colorretal é a causa mais comum de estenoses retais. A isquemia do local da anastomose, donuts (anéis) incompletos de anastomose grampeada e infecção pélvica são alguns dos fatores de risco que desempenham um papel no desenvolvimento de estenoses retais pós-operatórias. No entanto, o papel do estoma de desvio no desenvolvimento de estenoses retais não foi estudado extensivamente. Objetivos Estudar a diferença na ocorrência de estenoses anastomóticas (EA) em pacientes submetidos à ressecção anterior baixa (LAR) com ileostomia de proteção e a LAR sem ileostomia de proteção para carcinoma de reto. Métodos Este foi um estudo prospectivo e comparativo de caso-controle realizado em um centro de referência de atenção terciária. A ressecção anterior baixa com ileostomia de proteção foi realizada em pacientes com carcinoma de reto no grupo de estudo, enquanto LAR sem ileostomia de proteção foi realizada no grupo controle. O grupo de estudo tinha 29 pacientes, enquanto o grupo controle tinha 33 pacientes com carcinoma de reto. Resultados Durante o período de acompanhamento médio de 9, 1 meses, 8 (28%) pacientes no grupo de estudo e 2 (6%) pacientes no grupo controle desenvolveram EA (p=0,019). Destes 8 pacientes com EA no grupo de estudo, 50% tinham EA de Grau I, 25% tinhamEA de Grau II, enquanto 25% dos pacientes tinham EA de Grau III (grave). No entanto, ambos os pacientes que desenvolveram EA no grupo de controle tinham um tipo leve (Grau I) de EA. Conclusão A ileostomia de proteção aumenta as chances de formação de AS após LAR para carcinoma de reto. Além disso, o SKIMS Clinical Grading of Rectal Strictures é uma ferramenta simples e útil disponível para cada cirurgião para graduar, classificar e monitorar as estenoses retais pós-operatórias.

The effective transfection of a low dose of negatively charged drug-loaded DNA-nanocarriers into cancer cells via scavenger receptors / 药物分析学报

DNA-nanotechnology-based nano-architecture scaffolds based on circular strands were designed in the form of DNA-nanowires(DNA-NWs)as a polymer of DNA-triangles.Circularizing a scaffold strand(84-NT)was the critical step followed by annealing with various staple strands to make stiff DNA-triangles.Atomic force microcopy(AFM),native polyacrylamide gel electrophoresis(PAGE),UV-analysis,MTT-assay,flow cytometry,and confocal imaging were performed to assess the formulated DNA-NWs and cisplatin(CPT)loading.The AFM and confocal microscopy images revealed a uniform shape and size distribution of the DNA-NWs,with lengths ranging from 2 to 4 μm and diameters ranging from 150 to 300 nm.One sharp band at the top of the lane(500 bp level)with the loss of electrophoretic mobility during the PAGE(native)gel analysis revealed the successful fabrication of DNA-NWs.The loading efficiency of CPT ranged from 66.85％to 97.35％.MTT and flow cytometry results showed biocompatibility of the blank DNA-NWs even at 95％concentration compared with the CPT-loaded DNA-NWs.The CPT-loaded DNA-NWs exhibited enhanced apoptosis(22％)compared to the apoptosis(7％)induced by the blank DNA-NWs.The release of CPT from the DNA-NWs was sustained at＜75％for 6 h in the presence of serum,demonstrating suitability for systemic applications.The IC50 of CPT@DNA-NWs was reduced to 12.8 nM CPT,as compared with the free CPT solution exhibiting an IC50 of 51.2 nM.Confocal imaging revealed the targetability,surface binding,and slow internalization of the DNA-NWs in the scavenger-receptor-rich cancer cell line(HepG2)compared with the control cell line.

"PNR-Bleed" classification and Hemorrhoid Severity Score-a novel attempt at classifying the hemorrhoids / Classificação "PNR-Bleed" e escore de gravidade das hemorróidas - uma nova tentativa de classificação de hemorróidas

ABSTRACT Hemorrhoids are the most common anorectal disorders with a prevalence of 39% in general population. Hemorrhoids are generally classified on the basis of their location and degree of prolapse. Goligher's classification does not describe the number of hemorrhoidal columns involved and does not give much consideration to the amount of blood loss. To describe the hemorrhoidal disease more vividly, we devised the "PNR-Bleed" (or PNR-Booking) classification system. We tried to classify the hemorrhoids based on the four main characteristics of the hemorrhoidal disease i.e. the degree of hemorrhoidal Prolapse (P), Number (N) of the primary hemorrhoidal columns involved, Relation (R) of the hemorrhoidal tissue to dentate line and the amount of Bleeding (B) from it. All the four components in this classification system are graded into five grades ranging from 1 to 5. The peculiarity of this new classification system is that it allows more detailed documentation of the hemorrhoids in a particular patient and conveys more explicit meaning and information about the hemorrhoids for future references. Based on this 'PNR-Bleed' classification, we are introducing another concept of scoring the severity of hemorrhoids and referred it as the Hemorrhoid Severity Score (HSS). Hemorrhoid Severity Score (HSS) is the total score obtained by the sum of the numerical grades of all four characteristics of hemorrhoids in "PNR-Bleed" classification. This new "PNR-Bleed" system of classifying the hemorrhoids and calculation of HSS seems to be more comprehensive, detailed, more objective and easily reproducible.

RESUMO As hemorróidas são os distúrbios anorretais mais comuns, com uma prevalência de 39% na população em geral. As hemorróidas são geralmente classificadas com base em sua localização e grau de prolapso. A classificação de Goligher não descreve o número de colunas hemorroidais envolvidas e não dá muita importância à quantidade da perda de sangue. Para descrever a doença hemorroidária de maneira mais precisa, criamos o sistema de classificação "PNR-Bleed" (ou PNR-Booking). Tentamos classificar as hemorróidas com base nas quatro principais características da doença hemorroidária, isto é, o grau de prolapso da hemorroida (P), número (N) das colunas hemorroidais primárias envolvidas, a relação (R) do tecido hemorroidário para a linha denteada e a quantidade de sangramento (B) originando-se dele. Todos os quatro componentes deste sistema de classificação são classificados em cinco graus, variando de 1 a 5. A peculiaridade desse novo sistema de classificação é que ele permite uma documentação mais detalhada das hemorróidas em um paciente em particular e transmite o significado e informações mais explícitos sobre as hemorróidas. para referências futuras. Com base nessa classificação "PNR-Bleed", estamos introduzindo outro conceito para o escore da gravidade das hemorróidas e denominado HSS, de "Hemorrhoid Severity Score". O escore de gravidade da hemorroida (HSS) é o escore total obtido pela soma dos graus numéricos de todas as quatro características das hemorróidas na classificação "PNR-Bleed". Esse novo sistema "PNR-Bleed" de classificação de hemorróidas e cálculo do HSS parece ser mais abrangente, detalhado, mais objetivo e facilmente reproduzível.

Ameliorative effect of hydro-methanolic extract from roots of Rauwolfia serpentina on some biochemical parameters of type 1 diabetic mice

Present work seeks to investigate the biochemical parameters in terms of hypoglycemic and hypolipidemic effects of hydro-methanolic roots extract [HyMREt] of Rauwolfia serpentina in type 1 [alloxan induced] diabetic mice. Animals were divided into seven groups, four control groups, and three were test groups [HyMREt at 50, 100, and 150mg/kg]. Each treatment was repeated for 14 days regularly in all seven respective groups and afterwards the body weights, fasting blood glucose [FBG], insulin, and serum lipid levels were determined. Total body weights of diabetic mice treated with HyMREt extract were dose dependently [p

Homeostasis model assessment of insulin resistance in non-diabetic heart failure patients: a case-control investigation at tertiary care Hospitals of Karachi

Heart failure is a progressive, chronic disorder. Insulin resistance [IR] has been more and more involved as a preliminary metabolic perturbance predisposing to hyperglycemia, hyperlipidemia and atherosclerosis with others heart diseases. To investigate the relation of insulin resistance [IR] in non-diabetic heart failure patients this case-control study was carried out to ascertain the presence of IR with the aid of Homeostasis Model Assessment of Insulin Resistance [HOMA-IR] in non-diabetic heart failure patients [NDHF patients] compared with healthy controls. The sample size was calculated for both, cases [NDHF patients] and control [healthy subjects], which was initially consisted of 113 respondents each. The study consisted of two phase duration. In Phase I, NDHF patients were approached initially; only 80 patients with NDHF completed the study procedure. In Phase II, 80 healthy subjects were targeted and matched. Fasting blood glucose level [FBGL] and serum insulin was estimated. Mathematical model to quantify beta-cell function and insulin resistance was also computed through Homeostasis Model Assessment of Insulin Resistance [HOMA-IR] in both groups. Data was analyzed on SPSS version 16. Mean values with +/- standard deviation [SD] of insulin [10.2+/-4.36] and HOMA-IR [2.52+/-1.15] were significantly [p <0.05] higher in NDHF patients as compared to control subject [6.4+/-3.39, 1.45+/-0.80]. Average insulin to glucose ratio was 0.10+/-0.044 in NDHF patients which was significantly [p <0.0001] lowered in controls i.e., 0.073+/-0.039. Marginal and matrix plot analysis revealed that a higher patients count have had the HOMA-IR values <1.5 units while opposite scenario was observed in control group. Regression analyses of HOMA-IR with FBGL [as independent indicator] also authenticate the similar pattern. The present study concludes that insulin resistance [decreased insulin sensitivity] is a characteristic finding in Pakistani population of heart failure as compared to matched healthy controls

Brachdactyly instigated as a result of mutation in GDF5 and NOG genes in Pakistani population

Objectives: Brachdactyly a genetic disorder associated with the abnormal development of metacarpals, phalanges or both which results in the shortening of hands and feet. Mutations in the contributing genes has been recognized with the majority of the investigated syndromic form of brachdactyly. The current study was proposed to examine mutation in NOG and GDF5 genes in a Pakistani family

Methods: Poly Acrylamide Gel Electrophoresis and Polymerase Chain Reaction was used for the genomic screening and linkage analysis to observe the mutation in genes. The samples were collected from Luckki Marwat district, KPK, while the research study was conducted in the department of Biochemistry, Quaid-IAzam University, Islamabad, Pakistan

Results: After survey, family was identified with brachdactyly type A2 and investigated a heterozygous arginine to glutamine exchange in the growth demarcation factor 5 in all the victim persons. Different types of skeletal dysplasia resulted due to mutation in the GDF5 genes. Novel GDF5 genes mutations were reported with distinct limb malformation and sequencing of coding region revealed that the mildly affected individuals were heterozygous while the harshly affected individuals were homozygous

Conclusion: The current study reported the genetic variability and concluded that the Brachdacytyly type A2 and type B2 resulted due to mutation in GDF5 and NOG genes respectively. A new subtype of brachydactyly [BDB2] was instigated as a result of novel mutations in NOG. The mutation has been reported for the first time in Pakistani population and especially in Pushtoon ethnic population

Ethanolic seeds extract of Centratherum anthelminticum reduces oxidative stress in type 2 diabetes

This work was accomplished to assess the in-vitro antiglycation and antioxidant activities of ethanolic seeds extract of Centratherum anthelminticum [CSEt], followed by its in-vivo examination in type 2 diabetes. Overnight fasted rabbits were divided into control and diabetic groups. Rabbits in diabetic group were fed with 35% fructose solution to develop hyperglycemia that was well-monitored by glucometer. These were divided into diabetic control [distilled water 1ml/kg], positive control group [pioglitazone 15mg/kg] and two test groups [CSEt 400 and 600mg treated]. All treatments were given orally. After 14 days, rabbits were sacrificed and blood samples were used to estimate glycated haemoglobin [HbA1c] while total bilirubin [direct and indirect], uric acid, alanine aminotransferase [ALT] and creatine kinase [CK] were done in sera. In addition, antioxidant parameters viz., catalase [CAT], superoxide dismutase [SOD], reduced glutathione [GSH] and lipid peroxidation [LPO] were in liver tissues. The in-vitro studies showed good antiglycation and antioxidant potential of CSEt. Similarly, in-vivo investigation showed significant reduction in glycemia and body weights in type 2 diabetic test groups. Plus values of HbA1c, ALT, CK, uric acid and bilirubin were almost back to normal along with improvement found in efficiency of antioxidant parameters

Hypoglycemic and hypolipidemic activities of crude seeds of Centratherum anthelminticum in healthy volunteers and type 2 diabetic patients

This study first time reports the hypoglycaemic activity of crude seeds powder [CSP] of Centratherum anthelminticum in healthy and type 2 diabetic volunteers. In addition, hypolipidemic effect of same CSP was also determined in healthy volunteers. Healthy individuals were divided into control and two test groups T1 and T2 treated with 200 and 400mg of CSP. Similarly, type 2 diabetic patients were also divided into positive control [PC] treated with metformin 600mg and two test groups DT1 [CSP 400mg + metformin 600mg] and DT2 [CSP 400mg]. Each group has 6 individuals and each treatment was done orally. CSP 400mg was found more hypoglycaemic on all time intervals from 30 to 120min when oral glucose tolerance test was conducted in healthy volunteers. Both test quantities of CSP 200 and 400 mg were found successful in same healthy personsin decreasing the levels of triglycerides and total cholesterol [p<0.05], low and very low density lipoprotein cholesterols [p<0.01] and keeping the level of high density lipoprotein cholesterol as same as it was observed in control group. Similarly, CSP 400mg along with metformin and alone was also found helpful in lowering the fasting blood glucose levels in type 2 diabetic patients [DT1 and DT2] -24.99% and -20.62% respectively as compared to diabetic group only treated with metformin [PC], [p<0.01]. Therefore, CSP of C. antheminticum proves effective hypoglycaemic and hypolipidemic agent by possibly inducing glucose tolerance in healthy individuals and type 2 diabetic patients

Histological effects of nigella sativa on aspirin-induced nephrotoxicity in albino rats

Objective: To determine the histological effects of Nigella sativa on kidneys against aspirin-induced nephrotoxicity in albino rats. Study Design: An experimental study. Place and Duration of Study: Anatomy Department, University of Health Sciences, Lahore, from January 2014 to December 2015

Methodology: Thirty-two rats were equally divided into four groups A, B, C and D of eight animals each. Group A [control] was provided with single oral dose of 10 mg/100 gm body weight of 1% methyl cellulose. Group B [experimental group] and C [self recovery group] were provided with single oral dose of 1000 mg/kg aspirin. Group D was provided with 250 mg/kg ethanolic extract of Nigella sativa followed by 1000 mg/kg aspirin by oral gavage, after that only extract of Nigella sativa was given for seven days. Animals of groups A, C and D were sacrificed on the 8th day of experiment and that of group B on the second day of experiment. Kidneys were excised and fixed in 10% formalin solution. Hematoxylin, eosin and periodic acid Schiff's reagents were used to stain the kidney tissues. Histological slides were prepared to study proximal convoluted tubules

Results: Histological parameters were normal in control group A. Significant impairment was present in group B. There was no self-recovery in group C. Significant improvement was present in all the parameters of group D

Conclusion: Nigella sativa has protective effect on aspirin-induced nephrotoxicity in rats

Aspirin-induced nephrotoxicity in albino rats

Objective: To determine the histological effects of Nigella sativa on kidneys against aspirin-induced nephrotoxicity in albino rats

Study Design: An experimental study

Place and Duration of Study: Anatomy Department, University of Health Sciences, Lahore, from January 2014 to December 2015

Methodology: Thirty-two rats were equally divided into four groups A, B, C and D of eight animals each. Group A [control] was provided with single oral dose of 10 mg/100 gm body weight of 1% methyl cellulose. Group B [experimental group] and C [self recovery group] were provided with single oral dose of 1000 mg/kg aspirin. Group D was provided with 250 mg/kg ethanolic extract of Nigella sativa followed by 1000 mg/kg aspirin by oral gavage, after that only extract of Nigella sativa was given for seven days. Animals of groups A, C and D were sacrificed on the 8th day of experiment and that of group B on the second day of experiment. Kidneys were excised and fixed in 10% formalin solution. Hematoxylin, eosin and periodic acid Schiff’s reagents were used to stain the kidney tissues. Histological slides were prepared to study proximal convoluted tubules

Results: Histological parameters were normal in control group A. Significant impairment was present in group B. There was no self-recovery in group C. Significant improvement was present in all the parameters of group D

Conclusion: Nigella sativa has protective effect on aspirin-induced nephrotoxicity in rats