Design and synthesis of a novel cationic thiolated polymer

The purpose of this study was to design and characterize a novel cationic thiolated polymer. In this regard a hydroxyethylcellulose-cysteamine conjugate (HEC-cysteamine) was synthesized. Oxidative ring opening with periodate and reductive amination with cysteamine were performed in order to immobilize free thiol groups to HEC. The resulting HEC-cysteamine displayed 2035 ± 162 μmol immobilized free thiol groups and 185 ± 64 μmol disulfide bonds per gram of polymer being soluble in both acidic and basic conditions. Unlike the unmodified HEC, in case of HEC-cysteamine, a three-fold increase in the viscosity was observed when equal volumes of the polymer were mixed with mucin solution. Tablets based on HEC-cysteamine remained attached on freshly excised porcine mucosa for 8 0h and displayed increased disintegration time of 2h. Swelling behavior of HEC-cysteamine tablets in 0.1M phosphate buffer pH 6.8 indicated swelling ratio of 19 within 8h. In contrast, tablets comprising unmodified HEC detached from the mucosa within few seconds and immediately disintegrated. In addition, they did not exhibit swelling behavior. The transport of rhodamine 123 across freshly excised rat intestine enhanced by a value of approximately 1.6-fold (p-value = 0.0024) in the presence of 0.5% (m/v) HEC-cysteamine as compared to buffer control. Result from cytotoxicity test of HEC-cysteamine applied to Caco-2 cells in concentration of 0.5% (m/v) revealed 82.4 ± 4.60% cell viability. According to these results, HEC-cysteamine seems to be a promising polymer for various pharmaceutical applications especially for intestinal drug delivery.     

Brain antioxidant markers, cognitive performance and acetylcholinesterase activity of rat: Efficiency of Sonchus asper

ABSTRACT: BACKGROUND: Sonchus asper (SA) is traditionally used as a folk medicine to treat mental disorders in Pakistan. The aim of this study was to investigate the effect of polyphenolic rich methanolic fraction of SA on cognitive performance, brain antioxidant activities and acetylcholinesterase activity in male rats. METHODS: 30 male Sprague-Dawley rats were equally divided into three groups in this study. Animals of group I (control) received saline (vehicle), group II received SA (50 mg/kg) body weight (b.w.), and group III treated with SA (100 mg/kg b.w.,) orally in dimethyl sulphoxide (DMSO) for 7 days. The effect of SA was checked on rat cognitive performance, brain antioxidatant and acetylcholinesterase activities. Evaluation of learning and memory was assessed by a step-through a passive avoidance test on day 6 after two habituation trials and an initial acquisition trial on day 5. Antioxidant potential was determined by measuring activities of superoxide dismutase (SOD), catalase (CAT), contents of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) in whole-brain homogenates. Acetylcholinesterase (AChE) activity was determined by the colorimetric method. RESULTS: Results showed that 100 mg/kg b.w., SA treated rats exhibited a significant improvement in learning and memory (step-through latency time). SA administration reduced lipid peroxidation products and elevated glutathione levels in the SA100-treated group. Furthermore, salt and detergent soluble AChE activity was significantly decreased in both SA-treated groups. Short-term orally supplementation of SA showed significant cognitive enhancement as well as elevated brain antioxidant enzymes and inhibited AChE activity. CONCLUSION: These findings stress the critical impact of Sonchus asper bioactive components on brain function. KEYWORDS: Sonchus asper, Cognitive performance, Acetylcholinesterase activity, Antioxidant enzymes.     

Profile of poisoning admissions in Malaysia

We retrospectively reviewed poisoning admissions to all government health facilities from 1999 to 2001, in an effort to expand our current knowledge on poisoning in Malaysia to a level that better reflects a nationwide burden. There were 21 714 admissions reported with 779 deaths. The case-fatality rate was 35.88/1000 admissions. The majority of admissions (89.7%) and deaths (98.9%) occurred in adults. Some 55.1% of all admissions were female, mostly involving pharmaceutical agents. Male poisoning admissions were more often due to chemical substances. The prevalence of poisoning and death was highest among Indians compared to all other races in Malaysia. Overall, the majority of poisoning admissions were due to pharmaceutical agents, with agents classified as non-opioid analgesics, anti-pyretics and anti-rheumatics the most common. Pesticides accounted for the largest number of fatalities. It was also the commonest substance reported in cases of intentional self-harm. Most cases of poisoning admissions occurred due to accidental exposure (47%), followed by cases of intentional self-harm (20.7%). Overall, this study has managed to contribute substantial additional information regarding the epidemiology of poisoning in Malaysia, highlighting important issues, such as the rampant poisonings involving pesticides and analgesics, as well as the high prevalence of poisoning among Indians in Malaysia.     

Benign teratoma of the liver: a rare cause of cholangitis

Teratomas are neoplasms characterised by an abnormal growth of tissues derived from the three germinal layers. The term 'teratoma' is derived from the Greek root 'teratos', meaning monster. Germ cells develop in the embryo and subsequently become the cells that make up the reproductive system. During fetal development, these cells follow a midline path and descend into the pelvis as ovarian cells or the scrotal sac as testicular cells. The presence of germ cells in extragonadal sites is because of the failure of these cells to migrate along the urogenital ridge. Therefore, teratomas occur in order of decreasing frequency in the ovaries, testes, anterior mediastinum, retroperitoneum, sacrococcygeal region and cranium.Liver teratomas are very rare; of the 25 hepatic teratomas described in the literature, only five have occurred in adults. The majority of the cases were in female children below the age of three, mostly arising in the right lobe of liver.We report a case of an adult male with benign mature teratoma arising in the left lobe of liver, compressing the common bile duct and causing obstructive jaundice.     

Estimation of flavoniods,antimicrobial, antitumor and anticancer activity of <Emphasis Type="Italic">Carissa opaca</Emphasis> fruits

Background

Carissa opaca Stapf ex Hanes fruits is traditionally used in the treatment of asthma, hepatitis and microbial infections. The present study was arranged to investigate the antimicrobial, cytotoxic and antitumor activity of various fractions of C. opaca extract and its bioactive metabolites responsible for that activity.

Methods

To characterize various fractions of C.opaca antibacterial, antifungal, cytotoxic and antitumor assays are used. Eight strains of bacteria including Bacillus subtilis, Enterobactor aerogenes, Escherichia coli, Klebsiella pneumoniae, Micrococcus luteus, Pseudomonas aeroginosa, Salmonella typhy, and Staphylococcus aureus and four strains of fungal viz: Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger and Fusarium solani are used. Brine shrimps and potato dics are used for anticancer and antitumor potency of extract. High performance liquid chromatography (HPLC) is utilized for determination of bioactive metabolites responsible for the activity.

Results

HPLC chromatogram revealed the presence of orientin, isoquercetin, myricetin and apigenin. Various fractions of C. oapca showed significant antibacterial, antitumor and anticancer activity. In case of C. opaca fruit inhibition growth of Aspergillus niger was ranged between 23.2?±?1.36% to 43.3?±?2.39%, Aspergillus flavus ranged between 27.6?±?1.39% to 65.6?±?3.44%, Aspergillus fumigatus ranged between 13.2?±?1.00% to 52.4?±?1.54% and Fusarium solani ranged between 10.5?±?1.02% to 14.6?±?1.74%.

Conclusion

It can be concluded that, various fractions of C.opaca are accessible source of ethno pharmacy as they are consumed in different areas of Pakistan with ultimate health compensations.

     

Protective effect of Sonchus asper extracts against experimentally induced lung injuries in rats: A novel study

In this study, protective effects of methanol extract (SAME) were evaluated against carbon tetrachloride induced oxidative stress in lungs. Male Sprague–Dawley rats were orally fed with various doses (100, 200 mg/kg body weight) of SAME and (50 mg/kg body weight) of rutin after 48 h of CCl₄ treatment (3 ml/kg body weight, 30% in olive oil) biweekly for 4 weeks. The results showed that administration of extracts and rutin significantly restored lung contents of reduced glutathione and activities of catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, quinine reductase were reduced while lipid peroxide, hydrogen peroxide, nitrite, DNA fragmentation% and activity of γ-glutamyl transferase, increased by CCl₄, were reversed towards the control levels by the supplement of Sonchus asper extracts and rutin. Lung histopathology showed that S. asper extracts and rutin reduced the incidence of lung lesions induced by CCl₄ in rats. These results suggest that S. asper fractions and rutin could protect lung against the CCl₄-induced oxidative damage in rats.     

Polygenic risk scores for prediction of breast cancer risk in Asian populations

PurposeNon-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups.MethodsThe development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases).ResultsThe best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk.ConclusionPRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry.     

Large vestibular aqueduct syndrome

Large Vestibular Aqueduct Syndrome is a congenital malformation of the temporal bone characterised by early onset of sensorineural hearing loss and vestibular disturbance. Familial large vestibular aqueduct syndrome suggests autosomal recessive or X-linked inheritance and accounts for non-syndromic sensorineural hearing loss in these patients.