Anti-obesity effect and UHPLC-QTOF-MS/MS based metabolite profiling of Solanum nigrum leaf extract

Objective: To evaluate the antioxidant potential and pancreatic lipase inhibitory action of optimized hydroethanolic extracts of Solanum nigrum. Methods: Optimized extraction for maximum recovery of metabolites was performed using a combination of freeze-drying and ultrasonication followed by determination of antioxidant and antiobesity properties. The ultra-high performance liquid chromatography equipped with mass spectrometry was used to analyze metabolite profiling of Solanum nigrum. Computational studies were performed using molecular docking and electrostatic potential analysis for individual compounds. The hypolipidemic potential of the most potent extract was assessed in the obese mice fed on fat rich diet. Results: The 80% hydroethanolic extract exhibited the highest extract yield, total phenolic contents, total flavonoid contents along with the strongest 2,2-diphenyl-1-picrylhydrazyl scavenging activity, total antioxidant power, and pancreatic lipase inhibitory properties. The 80% hydroethanolic extract not only regulated the lipid profile of obese mice but also restricted the weight gain in the liver, kidney, and heart. The 80% hydroethanolic extract also reduced alanine transaminase and aspartate transaminase concentrations in serum. The effects of plant extract at 300 mg/kg body weight were quite comparable with the standard drug orlistat. Conclusions: Solanum nigrum is proved as an excellent and potent source of secondary metabolites that might be responsible for obesity mitigation.

Anti-obesity effect and UHPLC-QTOF-MS/MS based metabolite profiling of Solanum nigrum leaf extract

Objective: To evaluate the antioxidant potential and pancreatic lipase inhibitory action of optimized hydroethanolic extracts of Solanum nigrum. Methods: Optimized extraction for maximum recovery of metabolites was performed using a combination of freeze-drying and ultrasonication followed by determination of antioxidant and antiobesity properties. The ultra-high performance liquid chromatography equipped with mass spectrometry was used to analyze metabolite profiling of Solanum nigrum. Computational studies were performed using molecular docking and electrostatic potential analysis for individual compounds. The hypolipidemic potential of the most potent extract was assessed in the obese mice fed on fat rich diet. Results: The 80% hydroethanolic extract exhibited the highest extract yield, total phenolic contents, total flavonoid contents along with the strongest 2,2-diphenyl-1-picrylhydrazyl scavenging activity, total antioxidant power, and pancreatic lipase inhibitory properties. The 80% hydroethanolic extract not only regulated the lipid profile of obese mice but also restricted the weight gain in the liver, kidney, and heart. The 80% hydroethanolic extract also reduced alanine transaminase and aspartate transaminase concentrations in serum. The effects of plant extract at 300 mg/kg body weight were quite comparable with the standard drug orlistat. Conclusions: Solanum nigrum is proved as an excellent and potent source of secondary metabolites that might be responsible for obesity mitigation.

Rare bleeding disorders: spectrum of disease and clinical manifestations in the Pakistani population

Background@#Rare inherited coagulation factor deficiencies constitute an important group of bleeding disorders. A higher frequency of these disorders is seen in areas of high consanguinity.Our aim was to study the prevalence and spectrum of rare inherited bleeding disorders, characterize the severity of the deficiencies, identify different clinical manifestations, and evaluate different treatments provided. @*Methods@#This cross-sectional study was conducted in the Department of Haematology, Armed Forces Institute of Pathology Rawalpindi, between January 2014 and December 2018.A detailed history was taken, and an examination was performed. The signs and symptoms were noted, and the patients were diagnosed on the basis of a coagulation profile. The disease severity was assessed using factor assays. @*Results@#Among 2,516 patients with suspected coagulation disorders, 774 (30.8%) had an inherited bleeding disorder. Of the 774 patients, 165 (21.3%) had a rare bleeding disorder;91 (55.2%) of them were males, and 74 (44.9%) were females, with a male-to-female ratio of 1.2:1. The median patient age was 9 years 3 months. The most common disorder was factor VII deficiency (46 patients, 27.9%). The most common clinical presentation was bruising in 102 (61.8%) and gum bleeding in 91 (55.2%) patients. @*Conclusion@#The most common rare bleeding disorder in our population is factor VII deficiency. The prevalence of these bleeding disorders is high in our population due to a high number of consanguineous marriages.

Metabolite profiling and antidiabetic attributes of ultrasonicated leaf extracts of Conocarpus lancifolius

Objective: To profile the secondary metabolites and to evaluate the antidiabetic potential of hydroethanolic leaf extracts of Conocarpus lancifolius. Methods: The various hydroethanolic extracts of Conocarpus lancifolius leaf were prepared by ultrasonication assisted freeze-drying. Total phenolic contents, flavonoid contents, antioxidant activity, α-glucosidase and α-amylase inhibitions of leaf extracts were determined. The metabolite profiling was accomplished by UHPLC-Q-TOF-MS/MS analysis. The antidiabetic assessment of the most potent extract was carried out by measuring the hypoglycemic and hypolipidemic effect in the high fat diet-fed diabetic albino mice. The blood glucose level, haemoglobin, total cholesterol, high-density lipoproteins (HDL) and low-density lipoproteins (LDL) were determined. Results: The 60% ethanolic extract exhibited the highest phenolic and flavonoid contents of (349.39 ± 2.13) mg GAE/g dry extract and (116.95 ± 2.34) mg RE/g dry extracts, respectively, and the highest DPPH scavenging activity with an IC50 value of (32.87 ± 1.11) μg/mL. The IC50 values for α-glucosidase and α-amylase inhibitions were (38.64 ± 0.93) μg/mL and (44.80 ± 1.57) μg/mL, respectively. UHPLC-Q-TOF-MS/MS analysis confirmed the presence of gallic acid, ellagic acid, corilagin, kaempherol-3-O-rutinoside, caffeic acid derivative, isorhamnetin and galloyl derivatives in the 60% ethanolic extract. Plant extract at a dose of 450 mg/kg body weight reduced blood glucose level, total cholesterol, LDL and HDL, and increased haemoglobin in alloxan-induced diabetic mice, Conclusions: Conocarpus lancifolius leaves are proved as a good source of biologically functional metabolites and possess antidiabetic activity which may be further explored to treat diabetes.

Neurosyphilis, eyes don't see what mind doesn't know. An old treatable disease with white matter lesion just like multiple sclerosis in a young patient

Syphilis is a bacterial infection caused by spirochete bacterium treponemapallidum. It is transmitted from one person to another through direct contact during sexual intercourse. During pregnancy the infection can also pass from mother to her child. Men who have sex with men are showing fastest rise in syphilis cases. Highest risk populations are young adults aged between 15 to 25 years. Neurosyphilis can occur anytime during the course of syphilis, it was rampant in the preantibiotic era whereas in the modern world it is considered a disease of the past and is rarely seen. However it is resurfacing the medical literature with sporadic cases being reported from all over the world. Here we are reporting a young male who presented with spasticity and ataxia; on investigation he had white matter lesions on MRI in the brain and spinal cord. His CSF showed pleocytosis and his blood and CSF serology was positive for syphilis. The patient later on confirmed sexual contacts in the past hence diagnosis was confirmed and he responded very well to treatment with nearly complete recovery. It is of prime importance to consider this disease in neurological differential diagnosis so as to identify this disease as early as possible and to reduce the mortality risk associated with delayed diagnosis

Development and evaluation of mucoadhesive buccal tablet containing metronidazole for the treatment of periodontitis and gingivitis

The current study was designed to evaluate mucoadhesive buccal tablet containing metronidazole [MTZ] for local action aided by Hydroxypropylmethylcellulose K4M [HPMC] and Carbopol 940® [CP] as mucoadhesive polymers with other ingredients like sodium starch glycolate [SSG], polyvinyl pyrollidone K30 [PVP] as disintegrant and binders respectively. Formulations [F1-F8] were prepared by direct compression method and characterized for different physicochemical parameters. Results showed that the average weight and friability were within USP limits. Maximum mucoadhesive time was observed for F2 [14 hr] containing moderate amount of HPMC and CP used in the study. Up most mucoadhesive strength value was observed with F3 containing highest amount of HPMC used. Results indicated that high amount of HPMC was linked with the moderate to higher mucoadhesive strength and time. Maximum swelling index was observed in F7 [191.3%]. Only F1-F3 showed complete in vitro MTZ release within 3 hr. Formulations containing PVP released MTZ incompletely over time while SSG released earlier. Formulation F1 was considered best in terms of MTZ release [100.5%] with diffusion based Korsmeyer-Peppas release kinetics. Therefore, MTZ exhibiting best physicochemical characters in mucoadhesive buccal tablet was found in F1 containing HPMC and CP in amounts of 37.5 mg and 25 mg, respectively, for local action

Antioxidant activity, Hypoglycemic potential and metabolite profiling of Hyophorbe indica leaf extract

Current work was performed to evaluate antioxidant activity, ?-glucosidase inhibition, phytochemical profiling and in vivo hypoglycemic activity of freeze dried, ultrasonicated Hyophorbe indica leaf extracts. The highest total phenolic contents of 208.77 +/- 2.11 mg GAE/g DE and total flavonoid contents of 173.90 +/- 2.30 mg Rutin/g DE were obtained in 60% ethanol extract. The 60% ethanol extract exhibited maximum DPPH radical scavenging with IC50 value of 35.35 +/- 0.189microg/mL and total antioxidant power of 330.26 +/- 3.13 [ASE/g PE], respectively. The highest ?-glucosidase inhibition [IC50 36.52 +/- 0.08?g/mL] was also observed for 60% ethanol extract. The 60% ethanol extract at dose of 450 mg/kg body weight reduced blood glucose level of alloxan induced diabetic mice by 51.41% which was quite comparable with metformin [56.67%]. Twelve compounds namely citric acid, procyanidin B3, epicatechin, procyanidin B2, catechin, catechin derivative, procyanidin B1, apigenin-c-hexocide-c-hexocide, kaempferol, kaempferol derivative, quinic acid derivative and gallic acid have been identified by using UHPLC-Q-TOF-MS/MS in 60% ethanol extract

Diagnostic accuracy of cerebrospinal fluid adenosine deaminase in detecting Tuberculous Meningitis

Objective: To determine diagnostic accuracy of Cerebro Spinal Fluid [CSF] Adenosine De-Aminase [ADA] in detecting Tuberculous Meningitis [TBM] keeping CSF Polymerase Chain Reaction [PCR] for Mycobacterium Deoxy Ribonucleic Acid [DNA] as gold standard

Methods: This cross sectional validation study was conducted at Department of General Medicine of PNS Shifa Naval Hospital Karachi, Pakistan from Oct 2015 to Mar 2017 for a total duration of one and a half year. One hundred and thirty six patients were included. The diagnosis of TBM was based clinically on symptoms like fever, headache, altered mental state and signs of meningeal irritation with CSF findings of increased proteins, low glucose and lymphocytic pleocytosis. Lumbar puncture was done and approximately 4ml of CSF sample was withdrawn for analysis. Diagnosis of TBM was confirmed by doing CSF PCR test for mycobacterium tuberculosis DNA

Results:Total 136 patients were enrolled in this study. Mean age in our study was 47.09 +/- 12.80 years, whereas frequency and percentages of male and female patients was 102 [75 percent] and 34 [25 percent] respectively. The diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of CSF ADA level in detecting TBM was 71.32 percent, 84.21 percent, 95.45 percent, 98.97 percent and 53.85 percent respectively

Conclusion: The study concludes that diagnostic accuracy of CSF ADA in detecting TBM is high which is proposed as an investigation to differentiate it from other causes of meningitis in places where PCR test is not available

Antihyperglycemic effect of Conocarpus erectus leaf extract in alloxaninduced diabetic mice

Synthetic drugs have widely been helpful in management of diabetes mellitus type 2. However, side effects associated with synthetic drugs serve as an impetus to explore plants as alternate mode of treatment. The hydroethanolic leaf extracts of Conocarpus erectus were evaluated for phenolic contents, flavonoid distribution, antioxidant activity and antidiabetic potential. The maximum extract yield, total phenolic and flavonoid contents were exposed by 60% ethanolic extract. The Antioxidant and anti alpha-glucosidase tendency of 60% ethanolic extract was the most promising and complemented by in-vivo antihyperglycemic impact on mice. The findings were substantial regarding suppression of blood glucose levels in alloxan induced diabetic mice establishing the Conocarpus erectus as proficient pool of nutraceuticals for diabetes mellitus type 2 management

Primary mammary small cell carcinoma

Neuroendocrine breast cancer was defined in 2003 by WHO as a separate and unique breast cancer subtype. Primary small cell carcinoma of the breast, an exceptionally uncommon and aggressive tumor, is frequently characterised by early progression and worse outcome. Moreover, it is essential to distinguish between small cell carcinoma arising primarily in the breast and the metastatic disease to the breast. We had a patient of primary small cell carcinoma of breast. As her initial metastatic workup was negative for disease elsewhere, so she was started on neoadjuvant chemotherapy to which she responded well. Her modified radical mastectomy [MRM] was done followed by completion of chemotherapy up to 6 cycles and local radiotherapy of chest wall. However, the disease behaved aggressively afterwards as she developed recurrence twice at 9 and 19 months interval, respectively, for which she was considered for second and third line chemotherapy. An accurate management of the primary small cell carcinoma of the breast still lacks a consensus. Relevant studies were also reviewed to enhance knowledge and expertise in diagnosis, clinicopathologic features, management, and outcome of this tumor

Central nervous system [CNS] toxicity caused by metal poisoning: Brain as a target organ

People relate the neural disorders with either inheritance or psychological violence but there might be some other reasons responsible for the ailment of people that do not have such a background. The present study explains the chronic effect of heavy toxic metals on nervous system. During experimentation, rabbits used as laboratory animals, were given test metals in their diet. Concentration of metals given to them in the diet was less than their tolerable dietary intake. Behavioral changes were observed during experimentation. Periodic increase in the metal concentration was seen in the blood sample of rabbits. They were slaughtered after a period of eight months of slow poisoning. Histological examination of brain tissues was performed. The brain samples were analyzed by Atomic absorption spectroscopy and Inductively Coupled Plasma Mass Spectrometry to find the retention of heavy metals in mammalian brain. Concentration of lead, mercury and cadmium in the blood samples of occupationally exposed people and patients with neurological disorders at the time of neurosurgery was determined by using the same techniques. During circulation, toxic metals passes through the nerve capillaries to settle down in the brain. Heavy metals cross the blood brain barrier and 'may retain themselves in it. Brain tumors and biopsy samples of patients with neurological disorder were also analyzed to relate neurotoxicity and heavy metal poisoning. Results obtained shows that lead, mercury and cadmium retain themselves in the brain for longer period of time and are one of the causes of neurotoxicity

Comparison between metformin and insulin in treatment of gestational diabetes mellitus and effect on neonatal hypoglycaemia

To compare the efficacy of metformin in the treatment of gestational diabetes mellitus [GDM] with insulin and to compare the frequency of hypoglycaemia in neonates of the mothers treated with metformin and insulin. Randomized control trial to compare the efficacy of metformin with insulin in the treatment of GDM. Outpatient department and labour ward of Obstetric and Gynaecology department of Benazir Bhutto Hospital Rawalpindi from August 2012 to January 2013. A total of 110 pregnant ladies with GDM diagnosed after 20 weeks of gestation were included and divided into group A and group B with 55 patients in each group. Group A patients were treated with insulin and group B with metformin. Plasma fasting glucose and two hours postprandial glucose levels were determined on weekly basis for four weeks after starting the treatment to determine the efficacy of insulin and metformin. At birth plasma glucose levels of all the neonates were carried out two hourly, and more frequently depending upon the requirement, during first 24 hours in both the groups to determine neonatal hypoglycaemia. Fasting plasma glucose in group A and B were calculated as 5.96 +/- 0.58 and 5.76 +/- 0.46 mmol/L respectively [p=0.280], while two hours post-prandial plasma glucose levels were 7.34 +/- 0.48 and 7.28 +/- 0.58 mmol/L respectively [p=0.650]. Efficacy in group A was 78.18% and in group B was 70.91% [p=0.381] while frequency of neonatal hypoglycaemia was calculated as 61.54% in group A and 41% in group B [p=0.113]. The efficacy of metformin in treatment of gestational diabetes mellitus is similar as with insulin and the frequency of hypoglycemia in neonates of the mother treated with metformin and insulin is also similar

Conservative Management of Spinal Tuberculosis: Initial Series from Pakistan

STUDY DESIGN: A prospective study on spinal tuberculosis (TB) at a tertiary care hospital in an endemic region. PURPOSE: The aim of the study is to reiterate the importance of conservative management of spinal TB. OVERVIEW OF LITERATURE: Spinal tuberculosis can present with wide spectrum of symptoms, with back pain being the most common symptom. It is the leading cause of non-traumatic paraplegia in developing countries. There is an emerging trend to operate on patients early with spinal TB. METHODS: Forty-seven (M=14, F=33) patients were enrolled in the study during the four year study period. Initially, all the patients were subjected to computed tomography guided percutaneous needle aspiration (PCNA) followed by antituberculous therapy (ATT) for 12 months. Indications for surgery included patients with moderate to severe symptoms in which PCNA either failed, was impossible to carry out, or produced minimal improvement within 48 hours. RESULTS: Presenting complaints included pain (95.7%), weakness (85.1%) and sphincter involvement (12.8%). On the magnetic resonance imaging, a paravertebral abscess was seen in 37 (78.7%), disc and body destruction in 29 (61.7%), and an epidural abscess in 12 (25.9%) patients. Of the 47 patients, 9 (19.1%) required surgery, 4 of whom had failed PCNA attempts and 5 demonstrated indications despite successful PCNA. CONCLUSIONS: The results of conservative treatment consisting of PCNA and ATT for at least 12 months in compliant patients are excellent. A combined approach using clinical staging, PCNA, and ATT can minimize surgical intervention in most patients. However, ATT remains to be the cornerstone of management of spinal TB.

Oral aspects of chronic renal failure

Diseases such as diabetes mellitus, hypertension, chronic glomerulonephritis, uropathy and autoimmune diseases are considered the most frequent causes of renal failure. The aim of this study was to investigate oral manifestations caused by chronic renal failure. Oral manifestations of chronic renal failure include dysgeusia, stomatitis, decreased salivary flow rate, xerostomia and parotitis; moreover, dental oriented conditions include narrowing of pulp chamber, enamel abnormalities, tooth loss and periodontal disease. The most frequent dilemma in patients with Kidney failure is Renal Osteodystrophy. Chronic renal failure could be treated by renal replacement therapy, hemodialysis and peritoneal dialysis. These are methods of removing nitrogenous and other toxic byproducts of metabolized blood. Oral maladies due chronic renal failure occur because of immunosuppressive medications. However, this kind of therapy could be challenging as it causes gingival inflammation due to increased plaque deposition; which in turn affects the periodontal tissues. A good oral hygiene may reduce the risk of oral infections in chronic renal failure patients. The awareness about kidney related diseases is often neglected; however, the number of patients with oral manifestations related to chronic renal failure is miraculous

Various modes of fatalities and pattern of fatal injuries in the field

To determine various modes of fatalities and pattern of fatal injuries in the field. Descriptive study. The study was carried out at the Combined Military Hospital Bannu, the base hospital of Waziristan FATA from January 2005 to October 2009. All the soldiers brought in dead from operational area to CMH Bannu were included in the study. After entry of their personal data in admission and discharge book the detailed examination was carried out. Only percentages are presented for confidentiality purpose. However details may be provided by the author on requests routed through the authorities concerned. Gunshot wounds [33.51%], bomb blast [30.16%], mine blast [18.99%] and rocket blast [7.82%] were the common modes of fatality. Multiple injuries [two or more than two] were found on 63%, head injuries on 18%, chest injuries on 13% and abdominal injuries on 6% of all the fatal cases. Maximum numbers of fatal cases were received in the year 2005 [37.65%].Most common mode of fatal injuries was gunshot wound followed by bomb blast and mine blast. Multiple injuries were the most common fatal injuries followed by head and chest injuries. There is a need for preparedness at all levels to reduce the mortality.

frequency of hyperuricaemia and perinatal morbidity and mortality in Pakistani patients of pregnancy induced hypertension

To determine the frequency of hyperuricaemia in patients with pregnancy induced hypertension and to compare the early neonatal outcome between patients with hyperuricaemia and those without hyperuricaernia among patients with pregnancy induced hypertension. This is a descriptive case series study which was conducted in the Department of Obstetrics and Gynecology, Benazir Bhutto Hospital Rawalpindi, Pakistan from March 2011 to August 2011. One hundred and fifty pregnant women with pregnancy induced hypertension [defined as a BP > 140/90 diagnosed at the gestational age > 20 weeks on two separate occasions] were included by non-probability consecutive sampling in the labour room and the out patient department. These patients had their uric acid levels measured by Beckman Coulter Cx 9, fully automated chemistry analyzer using Beckman's uricase enzymatic, calorimetric, end point assay reagent. All patients underwent antenatal ultrasound with doppler studies in the last trimester to identify Intra Uterine Growth Retarded [IUGR] fetuses. These patients were followed till the time of delivery. The birth weight, NICU admissions and stillbirths/ intrauterine deaths were documented. The mean age of the patients was 27.48 +/- 4.3 years and the mean gestational age was 35 +/- 2.85 weeks. The uric acid level of the patients ranged from 148 to 755pmo1/L. The mean uric acid level of the patients was 372 +/- 106 pmol/L. Keeping the cutoff limit for hyperuricaemia as serum uric acid level > 325 pmol/L; we had 103 [68.7%] patients with hyperuricaemia. In the babies of these 103 patients, IUGR was seen in 99 [96.11%], IUD in 18 [17.48%], stillbirth in 2 [1.94%] and 72 [69.9%] were admitted to NICU. In the babies born to 47 patients who had no hyperuricaemia, IUGR was present in 32 [68.08%], 9 [19.14%] had IUD, 1 [2.12%] was stillbirth and 16 [34%] were admitted to NICU. Hence IUGR and admission to NICU were significantly more frequent among those with hyperuricaemia; p< 0.05. The mean birth weight of babies was 1.73 +/- 0.48 and 2.02 +/- 0.55 kg, respectively, among hyperuricaemic versus non-hyperuricaemic mothers; p= 0.002. Hyperuricaemia is frequent among patients with pregnancy-induced hypertension. Babies of patients with hyperuricaemia had significantly more IUGR, admission to NICU and significantly low birth weight

Adsorption of paracetamol on activated charcoal

In Vitro studies were carried out to investigate the adsorption activity of activated charcoal for paracetamol powder and tablets at pH 7.5. The effect of alcohol 6% [v/v] and methionine 0.1 [M] on the adsorption activity of activated charcoal for paracetamol was also investigated at pH 7.5 using charcoal to drug ratios as 4:1, 5:1, 6:1, 8:1, 10:1. The adsorption of paracetamol is fast and is 95.6% in 30 minutes. There was no effect on adsorption due to presence of alcohol 6% while methionine 0.1M has little effect on the adsorption of paracetamol as methionine competes for binding sites. It is concluded that activated charcoal is effective in adsorbing paracetamol. Methionine [sulphydryl] compound can be used as an antidote along with activated charcoal because of its negligible effect on adsorption of paracetamol