A network pharmacology approach to assess Reno-protective and -curative effects of methanolic extract of Malva neglecta Wallr in gentamicin induced renal toxicity rat model

Abstract The aim of present study was to explore protective and curative effects of Malve neglecta on kidneys. In silco study with network pharmacology was performed to find out potential target organs, genes and cellular cell lines which confirmed kidneys as target organ of phyto-constituents present in Malva neglecta extract. Gentamicin (40 mg/kg, i.p) was given to induce renal toxicity. Prophylactic study was performed with 300-, 600- and 900 mg/kg doses to find out nephro-protective and -curative effects and curative potential was evaluated at 900 mg/kg dose. Renal function biomarkers, blood urea, BUN, serum creatinine and uric acid, and oxidative stress measuring biomarkers, SOD, CAT, GSH and MDA levels in kidney homogenate were quantified at the end of study. Treatment groups showed decrease in blood urea, BUN, serum creatinine and uric acid levels dose dependently and curative group also showed decline in these biomarkers. SOD, CAT, GSH levels were increased and MDA level decreased in treatment groups significantly as compared to toxic control which revealed the role of oxidative stress in renal damage and anti-oxidant power of MN. Data suggested that use of MN along with drugs causing renal toxicity may prove beneficial due to its nephro- protective and curative effects.

Chemical characterization, docking studies, anti-arthritic activity and acute oral toxicity of Convolvulus arvensis L. leaves

Objective: To evaluate acute oral toxicity and anti-arthritic activity of the methanolic extract of Convolvulus arvensis L. leaves. Methods: Safety was assessed by acute oral toxicity (OECD 425) study. Anti-arthritic activity was explored by in vitro (inhibition of protein denaturation) and in vivo (Complete Freund's adjuvant-induced arthritis and carrageenan-induced inflammation) methods. Antioxidant potential was determined by assessing ferric reducing power, DPPH inhibition, and H2O2 scavenging assays. Furthermore, molecular docking was done to check interactions between the plant constituents and cyclooxygenases (COX-1 and COX-2). Quercetin, gallic acid, caffeic acid, syringic acid, sinapic acid, and vanillic acid were quantified by HPLC and eight compounds were identified by GC-MS analysis. Results: No mortality and abnormality in biochemical parameters were observed in the toxicity study. Histological analysis of vital organs also supported these biochemical results. The in vitro and in vivo studies showed that the methanolic extract of leaves of Convolvulus arvensis exhibited dose-dependent anti-arthritic and anti-oxidant potential. Molecular docking showed better interactions of plant compounds with cyclooxygenases as compared to standard ibuprofen. Conclusions: Convolvulus arvensis exhibits strong anti-arthritic activity, justifying the traditional use of the herbal drug.

Influence of Ozagrel Sodium along Atypical Anti-psychotic Drug on Red Blood Cell Distribution Width in Rats with Minimum and Maximum Dose Comparison

Objective: To study the activity of ozagrel sodium alone and in combination with the atypical antipsychotic drug on Red blood cell distribution width (RDW-CV) along with different doses and their comparison in rats. Method: This experimental study consisted of 120 albino rats of both gender, they were of 310-350 g, there were 10 groups which consists of each of 12 rats (n=12). Rats were treated with an accurate dose of ozagrel and atypical antipsychotic (Zuclopenthixol cis isomer of clopenthixol) alone and in combination for 3-weeks (21 days). We obtained blood sample at 0, 7th, 14th and last day of the study. Red blood distribution widths were measured from blood tests by utilizing standard medical laboratory technique. Red blood cell distribution width (RDW-CV) was measured by using the coefficient of variation indicator. Results were gathered and summarized by applying statistics. The comparison was formed between all days value to zero-day. Results: Minimum dose treated groups by both medications showed an increase and RDW-CV, but maximum dose showed p<0.001 decreases in RDW-CV in individual groups of drugs treatment and in case of RDW-CV maximum dose showed an increasing trend with p<0.001 in the combination groups. Conclusion: Maximum dose of ozagrel may cause a decrease in RDW-CV alone and it may cause an increase in (RDW-CV) with a combination of atypical antipsychotic drug.

Reviews of herbal and their secondary metabolites in the treatment of ulcerative colitis and peptic ulcer.

Peptic ulcer is a disease of the Gastro-intestinal tract (GIT), which includes both gastric and duodenal ulcers. The occurrence of peptic ulcer disease has been attributed to the imbalance between aggressive factors like acid, pepsin, and Helicobacter infection on one hand and the local mucosa defenses like bicarbonate and mucus secretion and prostaglandins synthesis on the other hand. The most serious complications of peptic ulcer disease include hemorrhage, perforation, penetration, and gastric outlet obstruction. Ulcerative colitis is a form of inflammatory bowel disease (IBD). It is a form of colitis, a disease of the colon that includes characteristic ulcers, or open sores. IBD is often confused with irritable bowel syndrome. Ulcerative colitis is associated with a general inflammatory process that affects many parts of the body. Sometimes these associated extra-intestinal symptoms are the initial signs of the disease, such as painful arthritic knees in a teenager and may be seen in adults also. Several classes of pharmacological agents have proved to be effective in the management of the acid peptic disorders viz., antacids, acid suppressive agents, anticholinergic, cytoprotective agents, etc. A widespread search has been launched to identify new anti-ulcer therapies from natural sources to replace currently used drugs of doubtful efficacy and safety. Herbs, medicinal plants, spices, vegetables and crude drug substances are considered to be a potential source to control various diseases including gastric ulcer and ulcerative colitis. In the scientific literature, a large number of medicinal plants and their secondary metabolites with anti-ulcer potential have been reported. As the gastro protective effect can be linked to different mechanisms, once demonstrated the activity, the extracts and more appropriately the active compounds should be assessed for action mechanisms to elucidate their mode of action. Besides, new action mechanisms may be discovered.

Fungi as chemical industries and genetic engineering for the production of biologically active secondary metabolites

Fungi is somewhere in between the micro and macro organisms which is a good source of producing biologically active secondary metabolites. Fungi have been used as tool for producing different types of secondary metabolites by providing different nutrients at different laboratory conditions. The fungi have been engineered for the desired secondary metabolites by using different laboratory techniques, for example, homologous and heterologous expressions. This review reported how the fungi are used as chemical industry for the production of secondary metabolites and how they are engineered in laboratory for the production of desirable metabolites;also the biosynthetic pathways of the bio-organic-molecules were reported.

Rationalization of Traditional Uses of Berberis lycium in Gastrointestinal Disorders.

Aims: Berberis lycium (Sumbal) is abundantly available in the northern areas of Pakistan and extensively used in local practice for the treatment of several human diseases. The objective of this study was to explore pharmacological basis for its use in gastrointestinal disorders. Materials and Methods: Crude aqueous (Bl.Aq) and methanolic (Bl.Meth) extracts of B. lycium were studied on isolated gut preparations of rabbit (jejunum) and guinea pig (ileum) by using in-vitro techniques. Tissues were mounted in tissue organ baths assembly containing physiological salt (Tyrode's) solution, maintained at 37ºC and aerated with carbogen, to assess the spasmogenic and spasmolytic effect and to find out the possible underlying mechanisms. Responses were measured on BioScience Powerlab data acquisition system by using isotonic transducers. Results: Phytochemical analysis indicates the presence of alkaloids, tannins and saponins in Bl.Aq and Bl.Meth. when tested on spontaneously contracting isolated rabbit jejunum, showed a dose-dependent spasmogenic effect at lower concentration (0.01-0.1 mg/mL) and (0.01-0.03 mg/mL), which was followed by spasmolytic effect at higher concentration (0.3-1.0 mg/mL) and (0.1-0.3 mg/mL) respectively. Pretreatment of the tissue with atropine (0.1 μM) partially suppressed the contractile effect. Bl.Aq and Bl.Meth caused complete inhibition of high K+ (80 mM)–induced contraction at 0.3 mg/mL and 0.1 mg/mL respectively and also produced a dose-dependent (0.01-0.03 mg/mL) rightward shift in the Ca++ concentration-response curve, similar to verapamil. When tested in bolus protocol on isolated guinea pig ileum, Bl.Aq and Bl.Meth caused a dosedependent spasmogenic effect at 0.01-0.1 mg/mL. Pretreatment of tissue with atropine (0.1 μM) partially suppress the contractile effect. Conclusions: Results indicate that spasmogenic effect was partially mediated through cholinergic activity and spasmolytic effect was mediated through calcium channel blocking activity (CCB), explain its traditional uses in diarrhea, intestinal cramps and other gastrointestinal intestinal disorders.

Teenage jejunoileal diverticulosis

Presentation of jeujunoileal diverticulosis in young age is virtually unknown. It is associated with middle or old age. It is usually asymptomatic but may present with vague abdominal pain and episodic nausea, vomiting or diarrhoea. It can lead to complications like bleeding, perforation and obstruction. We had 3 cases of jejuno-ileal diverticulosis presenting in their teens. They had resection and anastomosis resulting in improved health

Ethambutol resistance of indigenous Mycobacterium tuberculosis isolated from human patients

The present study was conducted to find out the ethambutol resistance pattern of indigenous isolates of Mycobacterium tuberculosis from Tuberculosis diagnosed human patients. A total of 172 specimens were collected from six different sources and comprised of 84.9 percent sputum, 10.5 percent pus and 4.7 percent bronchial washings. There were 70.9 percent males and 29.1 percent females with 84.30 percent pulmonary and 15.69 percent extra-pulmonary tuberculosis. The Mycobacterium tuberculosis isolates collected from primary culture were further studied to determine their pattern and level of resistance. The inoculums were prepared using 0.5 Mac Farland turbidity standards. Five different concentration of ethambutol were used in Lowenstein Jensen (LJ) medium i.e. 2μg/ml, 4μg/ml, 6μg/ml, 8μg/ml and 10μg/ml for sensitivity testing. Data showed 10 (5.8 percent) resistant and 162 (94.2 percent) sensitive Mycobacterium tuberculosis out of total 172 clinical isolates. The growth was not inhibited at 1st (2μg/ml) and 2nd (4μg/ml) drug levels, while growth of 50 percent isolates inhibited at 3rd level (6μg/ml), 30 percent inhibited at 4th level (8μg/ml) and 20 percent at 5th level (10μg/ml). The last three levels are above the therapeutic index and not recommended in actual clinical practice. It is thus conceivable to explore some other more effective chemotherapeutic agents, modify combinations or find more effective procedures to stop morbidity and mortality due to ethambutol resistant Mycobacterium tuberculosis.

Occult medullary thyroid carcinoma: an unusual presentation of carcinoma of the thyroid gland

A 33 years old male patient presented with slowly increasing painless swelling over left side of neck from 4 years, resulted in disfigurement. On examination it was a large firm, lobulated swelling extending from just left side of midline to anterior border of left trapezius, and from mandible to clavicle. It was not moving with swallowing. FNAC of the swelling was suggestive of metastatic follicular carcinoma of the thyroid gland. Serum TSH was normal. Radical lymph node dissection was done with total thyroidectomy. Histopathological examination showed it to be metastatic medullary carcinoma of the thyroid gland with microscopic primary in the left lobe of thyroid gland. All other examinations related to multiple endocrine neoplasia were normal

Damage control laparotomy for exsanguinating penetrating abdominal trauma

Damage control, defined as initial control of haemorrhage and contamination with intra-peritoneal packing and rapid closure, allows the resuscitation to normal physiology in the intensive care unit and subsequent definitive re-exploration. A case of penetrating abdominal trauma with extensive hepatic, interior vena cava and pancreatico-duodenal injuries, was managed on the principles of damage control on the first laparotomy and definitive procedure of pancreaticoduodenectomy was delayed and performed after 48 hours

Management of vascular trauma

To characterize the vascular injuries, their management and the results. Design: Descriptive study. Place and Duration of Study: Department of General Surgery, Combined Military Hospital, Kharian Cantonment, between October 2000 and October 2003. Subjects and Cases of vascular injuries received at the hospital amongst the total of 3134 trauma patients were evaluated. Thirty six cases with 41 vascular lesions were evaluated, excluding the three primary amputations. Vascular injuries were then characterized by age, gender, site, mechanism, associated injuries, need and type of surgery. Penetrating trauma accounted for 94.4% of all vascular admissions. Five% of the vascular injuries developed complications. Surgical intervention was required in all cases [100%]. Reverse saphenous vein graft was used in 82.9%. The injured veins were mostly ligated except one, which was managed by saphenous vein graft. The average time lapsed between injury and intervention of patients ranged between 2 to 18 hours. No mortality or secondary haemorrhage was documented. Vascular trauma represents a small percentage of all trauma admissions. It has a high morbidity and most require surgical intervention. The operative intervention rates are higher in patients with vascular injuries than in the general trauma population but with prompt surgery, the chances of limb salvage increases and the overall complication rate reduces

Human toxocariasis and ascariasis: concomitant parasitism in Srinagar, Kashmir, India.

Human toxocariasis caused by Toxocara canis is common in both developing and developed countries and leads to visceral larva migrans with high morbidity and mortality. Ascariasis caused by Ascaris lumbricoides, too has global distribution and in India, high prevalence rate has been reported in Kashmir (J & K State). Both nematode parasites, Toxocara canis and A. lumbricoides require similar biological and environmental conditions for the development of eggs in soil. Therefore, the present study was attempted to detect the antibody response to T. Canis excretory-secretory (ES) antigen by enzyme linked immunosorbent assay in patients attending Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir to assess the magnitude of human toxocariasis in Kashmir, the highly endemic area of ascariasis. Interestingly, it was observed that 38 (82.60%) out of 46 patients harbouring Ascaris Iumbricoides had positive antibody response to T. Canis ES antigen while none of the 15 normal healthy subjects from the same endemic zone, 25 from low endemic zone Chandigarh and 15 from other parasitic infections (hookworm, hydatidosis, cysticercosis) indicated detectable positive response. Majority of the ascariasis positive patients studied were in the age group of 21-40 years. However, one ascariasis patient studied in the age group of 1-10 years (4 years old) had also positive antibody response to T. Canis antigen. This study is the first report of human toxocariasis in Kashmir, India, an endemic zone for ascariasis and emphasizes the need for detailed epidemiological study for the ultimate prevention and control of this disease