Astragalus grahamianus extract: a novel source of bioactive compounds with antioxidant and neuroprotective activities.

The Astragalus grahamianus (AG) Royle ex. Benth is traditionally used for the treatment of various human disorders. The current research work is aimed to explore the neuroprotective anti-Parkinson effects of various fractions of Astragalus grahamianus (A. grahamianus). Fine powder of Astragalus grahamianus was extracted with 70% methanol and then fractionated with various solvents on the basis of polarity. Standard protocols were used to investigate the bioactive constituents present in the various plant fractions. In-vitro antioxidant potential of various fractions was checked using diverse free radicals. In-vivo rats model was used to determined the neuroprotective effects of methanol fraction of A. grahamianus. The results revealed that various fractions of A. grahamianus contain flavonoids, cardiac glycosides, steroids, gums, terpenes, proteins, and carbohydrates except chloroform fraction lake the presence of steroids, cardiac glycosides, gums and saponins, aqueous fraction of steroids, terpenoids, gums and saponins, n-Hexane fraction steroids, carbohydrates, alkaloids, gums and flavonoids. The highest amount of total phenolic contents was found in AGME (32.67 ± 2.3 mg GAE / g). The AGME also showed enhanced free radicals cations potential against DPPH, ABTS and H2O2, respectively. The correlation between AOA (antioxidant activity) and TPC (total phenolic contents) revealed to be substantial. Relative R2 values for ABTS, H2O2, and DPPH activity are 0.9974, 0.9845, and 0.9678, respectively. The in-vivo neuroprotective activities showed significant results. Our findings highlight significant antioxidant, and neuroprotective possessions of AGME attributed to powerful bioactive compounds.

Identification of three novel pathogenic mutations in cystathionine beta-synthase gene of Pakistani intellectually disabled patients.

BACKGROUND: Classical homocystinuria (HCU) is an autosomal recessive inborn error of metabolism, which is caused by the cystathionine-ß-synthase (CBS: encoded by CBS) deficiency. Symptoms of untreated classical HCU patients include intellectual disability (ID), ectopia lentis and long limbs, along with elevated plasma methionine, and homocysteine. METHODS: A total of 429 ID patients (age range: 1.6-23 years) were sampled from Northern areas of Punjab, Pakistan. Biochemical and genetic analyses were performed to find classical HCU disease in ID patients. RESULTS: Biochemically, nine patients from seven unrelated families were identified with high levels of plasma methionine and homocysteine. Targeted exonic analysis of CBS confirmed seven causative homozygous mutations; of which three were novel missense mutations (c.451G>T; p.Gly151Trp, c.975G>C; p.Lys325Asn and c.1039 + 1G>T splicing), and four were recurrent variants (c.451 + 1G>A; IVS4 + 1 splicing, c.770C>T; p.Thr257Met, c.808_810del GAG; p.Glu270del and c.752T>C; p.Leu251Pro). Treatment of patients was initiated without further delay with pyridoxine, folic acid, cobalamin, and betaine as well as dietary protein restriction. The immediate impact was noticed in behavioral improvement, decreased irritability, improved black hair color, and socialization. Overall, health outcomes in this disorder depend on the age and symptomatology at the time of treatment initiation. CONCLUSIONS: With personalized treatment and care, such patients can reach their full potential of living as healthy a life as possible. This screening study is one of the pioneering initiatives in Pakistan which would help to minimize the burden of such treatable inborn errors of metabolism in the intellectually disabled patients.

Enzyme-assisted bioremediation approach for synthetic dyes and polycyclic aromatic hydrocarbons degradation.

Environmental protection from emerging pollutants has become a significant challenge for mankind as an increasing number of contaminants, including synthetic dyes and polycyclic aromatic hydrocarbons (PAHs), represent a serious risk to ecological and environmental balance. Most synthetic dyes have complex aromatic structures and are resistant to degrade by classical approaches, such as physical and chemical processes, including adsorption, chemical coagulation, flocculation, ion exchange, membrane separation, froth flotation, and reverse osmosis. Enzymes-assisted catalytic transformation of pollutants has become a potential alternative to classical methods because of their ability to react with complex compounds, a quick degradation rate, and producing less harmful by-products. Plant peroxidases, and microbial laccase and lignin-degrading peroxidases (manganese and lignin peroxidase) have gained significant attention for treating aromatic waste due to their capability of oxidizing and detoxifying a wide range of recalcitrant xenobiotics, including PAHs and synthetic dyes. Peroxidases being efficient biocatalysts detoxify an array of toxic compounds by simple free-radical mechanism resulting in the formation of oxidized and depolymerized products of significantly reduced toxicity. Moreover, it is an ecofriendly and economically favorable approach towards the biodegradation of recalcitrant and toxic industrial waste. Among microbial and plant peroxidases, bacterial enzymes have broad substrate specificity and can transform a wide range of recalcitrant substrates. Ligninolytic enzymes oxidize the aromatic ring into quinones and acids by producing free hydroxyl radicals instead of dihydrodiols and mineralize aromatic hydrocarbon in combination with cytochrome P450, monooxygenases, and epoxide hydrolases. In the review, an attempt has been made to provide detailed knowledge about the availability of inexpensive peroxidases sources, their mechanism of action, and degradation potential. The present review summarizes the exploitation of peroxidases from plants, bacteria, and fungus (manganese peroxidase, lignin peroxidase, and laccases) for detoxification and degradation of textile dyes as well as PAHs. Conclusively, peroxidases have great potential to react with almost all classes of synthetic dyes and most PAHs due to broad substrate specificity and transformed them into less harmful metabolites.

Efficient removal of dyes using carboxymethyl cellulose/alginate/polyvinyl alcohol/rice husk composite: Adsorption/desorption, kinetics and recycling studies.

Rapid industrialization is polluting the water resources and is becoming a serious environmental issue. In present study, the adsorption-desorption behavior of Direct Orange-26 (DO-26), Direct Red-31 (DR-31), Direct Blue-67 (DB-67) and Ever direct Orange-3GL (EDO-3) dyes on to native, modified rice husk (MRH), polyvinyl alcohol (PVA), carboxymethyl cellulose (CMC) and alginate (ALG) immobilized biomasses were investigated under different experimental conditions. For adsorbent modification, physical and chemical treatments were performed. The results showed that HCl pre-treatment considerably increased the sorption capacity of dyes versus native biomass. The sorption data were optimized using pseudo 1st order, intra-particle diffusion, pseudo 2nd order and Elovich models. The results revealed that the two-step rate equation was followed for the desorption kinetics of dyes. The involvement of -OH (hydroxyl), -COOH (carboxylic) and -NH2 (amino) groups in the adsorption of dyes onto biomasses was shown by FTIR analysis. Studies exhibited that among adsorbents employed, the MRH has the excellent potential for the dyes degradation from textile effluents.

Surfactant Assisted Sonochemical Synthesis and Characterization of Gadolinium Doped Zinc Oxide Nanoparticles.

Pure and Gd doped Zinc Oxide (ZnO) nanoparticles were synthesized by sonochemical method using different surfactants (PVP/CTAB). The nanoparticles were characterized by powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), particle size analysis by DLS technique and UV-Visible spectroscopy. The effect of Gd doping and nature of surfactants on crystallite size, morphology and band gap of ZnO nanoparticles have been investigated. In addition to this, the effect of nature of surfactant on amount of dopant inserted in the ZnO lattice was also studied.

Solution thermodynamics and solubilization behavior of diclofenac sodium in binary mixture of Transcutol-HP and water.

Solution thermodynamics and solubilization behavior of diclofenac sodium (DS) in binary mixture of Transcutol-HP and water is not reported in the literature so far. Therefore, the aim of the present study was to investigate the solution thermodynamics and solubilization behavior of DS in mono-solvents and various Transcutol-water mixtures at 298.15-333.15 K. The mole fraction solubility of DS was determined by shake flask method and thermodynamic parameters (enthalpies and entropies) were calculated with the help of the modified Apelblat model. The experimental solubility data of DS in all sample matrices was found to be correlated well with the modified Apelblat model with correlation coefficients of 0.9950-0.9990. Absolute relative deviation was found to be less than 3% in most of the Transcutol-water mixtures at each temperature studied. The mole fraction solubility of DS was observed to be highest in pure Transcutol (0.139 at 298.15 K) as compared to pure water and other Transcutol-water mixtures. The enthalpies and entropies for DS dissolution were observed as positive values for all cosolvent mixtures which indicated that the dissolution of DS is endothermic and an entropy-driven process. Based on solubility data, DS was considered as sparingly soluble in pure water and freely soluble in Transcutol. These results indicated that Transcutol could be used as an alternate of ethanol, propylene glycol and polyethylene glycol to enhance aqueous solubility of DS. These preliminary studies could be useful in formulation development of DS especially in terms of liquid dosage forms and injectable formulations.

Drinking water: a major source of lead exposure in Karachi, Pakistan.

Excess lead in drinking water is a neglected source of lead toxicity in Pakistan. A cross-sectional survey in 2007/08 was made of water samples from drinking water sources in Karachi, a large industrial city. This study aimed to compare lead levels between untreated ground water and treated surface (tap) water in 18 different districts. Of 216 ground and surface water samples collected, 86% had lead levels higher than the World Health Organization maximum acceptable concentration of l0 ppb. Mean lead concentration in ground water [146 (SD 119) ppb] was significantly higher than in surface water [77.1 (SD 54) ppb]. None of the 18 districts had a mean lead level of ground or surface water below the WHO cut-off and ground water sources in 9 districts had a severe level of contamination (>150 ppb). Urgent action is needed to eliminate sources of contamination.

Aflatoxin B1 in chilies from the Punjab region, Pakistan.

The occurrence of aflatoxin B1 (AFB1) in chilies from Pakistan was determined by using HPLC in work undertaken in Pakistan. Whole (n = 22) and powdered (n = 22) chilies were analyzed. Sixteen (73.0%) and 19 (86.4%) samples of whole and ground chilies, respectively, were contaminated. The mean concentration in powdered chilies (32.20 µg/kg) was higher statistically than in whole chilies (24.69 µg/kg). Concentrations ranged from 0.00 to 89.56 µg/kg for powdered chilies, compared with 0.00-96.3 µg/kg for whole chilies. The limits of detection and quantification were 0.05 µg/kg and 0.53 µg/kg, respectively. The concentrations were high in general and greater than the statutory limit set by the European Union. There is considerable scope for improvements in chili production in Pakistan.

Microbial transformation of sesquiterpenoids.

Biotransformations are useful methods for producing medicinal and agricultural chemicals from both active and inactive natural products with the introduction of chemical functions into remote sites of the molecules. Research on microbial biotransformations of commonly available sesquiterpenoids into more valuable derivatives has always been of interest because of their economical potential to the perfume, food, chemical and pharmaceutical industries. Fungal transformations of sesquiterpenoids have been less frequently studied compared with many other natural products. In recent years, however, much attention has been given to the exploitation of new products with enhanced biological activity using microorganisms. This review, covering the period from 1990 to 2006, summarizes our knowledge of the biotransformations of sesquiterpenoids by various fungi. Such transformations could lead to the discovery of new reaction pathways that might be useful in the design of new value-added products.

Methicillin-resistant Staphylococcus aureus (MRSA) in hospitalized children: correlation of molecular analysis with clinical presentation and antibiotic susceptibility testing (ABST) results.

The molecular analysis of methicillin-resistant Staphylococcus aureus (MRSA) from 98 children admitted to the Children's Hospital of Michigan, Detroit, MI, with serious MRSA infections during 2006-2007 was correlated with risk factors, clinical features, and antibiotic susceptibility testing (ABST) results. Isolates were characterized by staphylococcal cassette chromosome (SCC) mec type, the presence of Panton-Valentine leukocidin (PVL) genes, repetitive sequence (rep) polymerase chain reaction (PCR) and pulsed-field gel electrophoresis (PFGE), requirement for surgical intervention, antibiograms, and response to therapy. rep-PCR was more rapid than PFGE typing and correlated well. SCCmec type IV-containing isolates caused 92.8% of all infections, but the demographics and diseases associated with subtypes IVa and IVd differed. Subtype IVa (all PFGE type USA300 and PVL-positive) was identified in 81/93 (87.1%) of patients with community-onset (CO) MRSA, including 21/35 of those with risk factors for health care-associated (HA) infection. All other clones were PVL-negative. Subtype IVd (10 isolates; 9 USA800 and 1 eMRSA15) caused mainly HA-MRSA and no skin and soft tissue infections (SSTI). Seven classic HA-MRSA strains (SCCmec types II [6; 3 USA100 and 3 USA600] and III [1; USA200]) caused HA and hospital-onset (HO) infections. Surgical intervention was required in 68/81 patients infected with USA300 and 8/17 of the others. Most USA300 were susceptible (S) to clindamycin (CD) and patients were treated with CD alone or in combination. The other isolates were generally treated with vancomycin (VA) alone or in combination.

Stressful life events, personal losses, and perimenopause-related depression.

We compared the number and quality of life events reported by depressed perimenopausal women and a non-depressed comparison group. Additionally, we examined the effects of the presence of hot flushes on life event reports. All women were 44-55 years old, had irregular menses and elevated plasma gonadotropin levels. The Psychiatric Epidemiology Research Interview recorded both the frequency of occurrence and the desirability of life events experienced by the women during the six months prior to the interview. Depressed perimenopausal women (n=50) reported significantly more undesirable events [Student's t-test (unpaired) with Bonferroni correction, t(98)=3.9, p=0.001] but not more exit events (e.g., divorce, last child leaving home or death in family) (t(98)=0.9, p=NS) compared to the non-depressed women (n=50). There were no effects of hot flushes on these diagnostic differences. The "empty nest" syndrome does not appear to be relevant in the development of perimenopausal depression. Nevertheless, independent of the presence of hot flushes, perimenopausal depressed women are more likely to report both negative life events and diminished self esteem.

Evaluation of hospitalized infants and young children with bronchiolitis - a multi centre study.

Four hundred and twenty nine young children with bronchiolitis admitted consecutively in different hospitals of Bangladesh were evaluated. Three hundred and forty eight children studied for their putative risk factors, clinical profile, management and the outcome. Both cases and controls were examined for respiratory syncytial virus (RSV) antibody status. The diagnosis of bronchiolitis was made on the basis of first attack of wheeze in previously healthy children below two years of age. Detailed history including the possible risk factors, the management and daily follow-up on the ward and the outcome at discharge were documented through a structured questionnaire. Chest x-ray was done in each case to find out the radiological changes. Blood of 266 patients and 30 controls were studied for RSV IgM and IgG antibody by ELISA. There were 66% male and 34% female children. The median age of the children was 3.0 months and 82.7% were below 6 months of age. Most of the babies were born term (88%), with ABW (73%), by normal vaginal delivery (88%). Exclusive or predominant breast-feeding were given in 72% cases. The location of the patient was rural in 55% cases. Around half of the parents were illiterate or slightly educated (up to 5 years schooling) fathers 46.5% and mothers 56% and majority of the parents were poor (74%). In 52% cases the number of family members in one room were four or more. Half of the parents (52%) were smokes and there was atopy in 26.5% families. The clinical features of bronchiolitis were mostly cough (99%), respiratory distress (97%), feeding difficulty (93%) and fast breathing (96%) (median RR 68/min). Fever (1000F or more) was in only 33% cases, though parents complained in 90% cases. All children (100%) had wheeze and crackles in lungs in 96% cases. Liver could be palpable in 83% and spleen in 42% cases. Important radiological features were increased translucency (96%), increased interstitial markings (87%), hyperinflation (75%) and streaky densities (61%). In 69.6% cases TLC was 12,000 or less and only 15% with a neutrophil fraction greater than 60%. Children were positive for IgM antibody in 43.6% cases and both IgM and IgG in 5.3% cases. The main modalities of treatment were antibiotics (99%) (Ampicillin, 76%), oxygen therapy (83%), nebulised salbutamol (76%) and intravenous fluid (51%). The median duration of hospital stay was 4 days. Most of the children were discharged with improvement (96%) with 2% mortality. Not a single case was diagnosed as bronchiolitis in hospitals outside Dhaka. Cefrtiaxone (72.5%) and parenteral steroids (70.5%) were the mainstay of therapy there.

Brain dysfunction following 'awake' craniotomy, brain mapping and resection of glioma.

The rationale for 'awake' resective brain tumour surgery and brain mapping is that the amount of tumour removed is optimized, and risks of damage to adjacent eloquent brain minimized by intraoperative patient assessments. Both goals are generally attained, but occasionally patients may have iatrogenic postoperative deficits. Five such cases (20%) are described from a consecutive series of 25 awake craniotomies. These patient fell into three distinct clinical categories; those (n = 2) who developed sensory-motor deficits that were recognized intraoperatively; those (n = 2) who had deficits that were apparent only on postoperative testing; and one patient who developed a sudden deficit with no warning. The former four patients had deficits that recovered within weeks to months (16%), but the latter one (4%) was left with a severe focal motor disability. These cases highlight both the benefits and limitations of awake craniotomy and intraoperative assessment. Although sensory-motor deficits can be recognized early, some high-level neurological functions may not be readily assessed intraoperatively and vascular catastrophes may occur without warning. The pathophysiological basis of these iatrogenic neurological deficits, and techniques to minimize such problems are discussed.

Basal plasma hormone levels in depressed perimenopausal women.

BACKGROUND: An association between abnormal changes in reproductive endocrine function during the perimenopause and the onset of depression in some women has been suggested but remains controversial. METHODS: We examined basal plasma hormone levels in two samples of women with well characterized, first onset depression (major or minor) during the perimenopause and matched comparison groups of asymptomatic women. Results were compared by analysis of variance. RESULTS: No significant diagnosis-related differences were observed in plasma hormone measures of the following: follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), estrone (E1), total (T) or free testosterone (FT), or the E2/LH ratio. We did identify significantly lower morning plasma dehydroepiandrosterone (DHEA) and its sulphated metabolite DHEA-S (but not cortisol) levels in the depressed women compared to the non-depressed comparison group. Women with hot flushes (regardless of the presence of depression) were significantly older than women without flushes, had significantly higher plasma levels of FT, LH and FSH, and had significantly lower E2/LH ratios. CONCLUSIONS: Women with first onset depression during the perimenopause are not distinguished from controls on the basis of basal hormone measures of ovarian estrogens, testosterone, or gonadotropins. However, perimenopause-related changes in E2 may interact with low levels of DHEA in some women to increase their vulnerability to develop depression. In contrast to perimenopause-related vasomotor symptoms, depression during the perimenopause is not associated with a simple hormone deficiency state. The relatively low levels of E2 and E1 in the depressed women may have met statistical significance in a much larger and homogenous sample.