ANTIOXIDANT AND ANTIBACTERIAL ACTIVITY OF ALKALOID EXTRACT OF CUCUMIS TRIGONUS ROXB

Objective: To evaluate the antioxidant and antibacterial efficiency of alkaloids of root, leaf, and fruit of Cucumis trigonus. Methods: The antioxidant and antibacterial properties of alkaloid extracts were assessed by ferric thiocynate (FTC), 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, hydrogen peroxide radical scavenging assay, superoxide radical scavenging activity and ferric reducing power were analyzed separately for its inhibition percentage at different concentration (20µg, 30µg, 40µg and 50µg/ml) and antibacterial activity by agar disc diffusion and minimum inhibitory concentration (MIC) against Staphylococcus aureus (MTCC Code-9886), Pseudomonas aeruginosa (MTCC Code-6458). Results: The highest percentage of extraction yield was observed in fruit followed by leaf and root. The maximum content of alkaloid was found in fruit and root compared to leaf. The scavenging efficiencies of the extracts increased with the increasing concentrations. Appreciable levels of total antioxidant activity by FTC (2.112±0.011%), DPPH radical scavenging activity (1.912±0.001%), superoxide radical scavenging activity (0.955±0.021%) and hydrogen peroxide radical scavenging activity (0.914±0.087 %) were observed at 50µg/ml of fruit extract. However, ferric reducing power was more in the root (0.893±0.0870%) compared to fruit (0.791±0.023%) and leaf (0.520±0.00 %) at 50µg/ml. The alkaloid extracts of root and fruit exhibited more antibacterial activity against Staphylococcus aureus (16.51±0.05 and 19.68±0.03 mm) and Pseudomonas aeruginosa (12.2±0.03 and14.2±0.06) at 100µg/ml than leaf. The minimum inhibitory concentration (MIC) of the root, leaf, and fruit was in the range of 3.125µg/ml to 35µg/ml for the pathogenic bacteria. Conclusion: Data from the present results revealed that the alkaloid extracts of fruit and root of C. trigonus show good antioxidant and antibacterial potential than leaf. Hence, may be explored for the formation of new antibacterial with antioxidant drugs

Significance of Mula Bandha for Urinary Incontinence in Women

Mula Bandha is the most important part of the Hatha yoga tradition. It is known as the ‘perineal lock’, contraction of the muscles around the perineal body in the male and the cervix in the female, in order to release and control energy generated by the mooladhara chakra. This lock affects the physical and psychic body.Leakage of urine is called urinary incontinence. Urinary incontinence is more common in women than in men and affects women of all ages. The underlying cause of urinary incontinence is pelvic floor weakness. In yoga, the pelvic floor exercise, or mula bandha, is one of the fundamentals of core body strength. The practice of mula bandha tones and strengthens the muscles of the pelvic region. Pregnancy and vaginal delivery are considered to be the main risk factors for the development of urinary incontinence in women because pregnancy and childbirth may cause damage to the fascias, ligaments, pelvic floor muscles, and nerves supporting and controlling the bladder neck and urethra. To prevent urinary incontinence, women have been encouraged to conduct pelvic floor exercises during pregnancy and after childbirth. Many research studies have found that the pelvic floor exercises were very effective in improving symptoms of Stress Urinary Incontinence

Acute kidney injury in obstetrics: a five-year study in a tertiary centre

Background: Pregnancy Related Acute Kidney Injury (PRAKI) is a major cause of maternal and foetal morbidity and mortality in developing countries. The incidence has declined due to improvements in reproductive health but it is still associated with significant perinatal mortality and maternal morbidity. It may be due to decrease in renal perfusion or ischemic tubular necrosis from a variety of conditions encountered during pregnancy. Our study aims at determining the predisposing factors and causes of AKI during pregnancy and its impact on maternal and foetal outcome.Methods: A retrospective cohort study over a period of 5 years was conducted on pregnant women with AKI as per inclusion and exclusion criteria. The detailed history, events, mode of delivery, cause leading to AKI, management, hospital stay, maternal and foetal outcome were studied in detail and evaluated. These patients were classified according to RIFLE criteria and were followed up for hospital stay and residual morbidities.Results: The incidence of PRAKI in the study was 0.07% (36 out of 50,735 deliveries) and among obstetric ICU patients, it was 6.8%. Most of the majority of the cases were unbooked (66.7%) and multipara (61.1%). Maternal morbidity was seen in 66.7% and mortality was 27.8%. Poor foetal outcome was seen in 44.4%.Conclusions: Haemorrhage is the most common cause of PRAKI, followed by toxaemia of pregnancy and sepsis. Early detection and meticulous management of haemorrhage, hypertension and sepsis reduce the incidence of PRAKI and associated maternal mortality

Chikungunya Infection in India: Results of a Prospective Hospital Based Multi-Centric Study

Chikungunya (CHIKV) has recently seen a re-emergence in India with high morbidity. However, the epidemiology and disease burden remain largely undetermined. A prospective multi-centric study was conducted to evaluate clinical, epidemiological and virological features of chikugunya infection in patients with acute febrile illness from various geographical regions of India.A total of 540 patients with fever of up to 7days duration were enrolled at Karnataka Institute of Medical Sciences (KIMS), Karnataka (South); Sawai Man Singh Medical College (SMS) Rajasthan (West), and All India Institute of Medical Sciences (AIIMS) New Delhi (North) from June 2008 to May 2009. Serum specimens were screened for chikungunya infection concurrently through RT-PCR and serology (IgM). Phylogenetic analysis was performed using Bioedit and Mega2 programs. Chikungunya infection was detected in 25.37% patients by RT-PCR and/or IgM-ELISA. Highest cases were detected in south (49.36%) followed by west (16.28%) and north (0.56%) India. A difference in proportion of positives by RT-PCR/ELISA with regard to duration of fever was observed (p<0.05). Rashes, joint pain/swelling, abdominal pain and vomiting was frequently observed among chikungunya confirmed cases (p<0.05). Adults were affected more than children. Anti-CHIK antibodies (IgM) were detected for more than 60days of fever onset. Phylogenetic analysis based on E1 gene from KIMS patients (n = 15) revealed ∼99% homology clustering with Central/East African genotype. An amino acid change from lysine to glutamine at position 132 of E1 gene was frequently observed among strains infecting children.The study documented re-emergence of chikungunya in high frequencies and severe morbidity in south and west India but rare in north. The study emphasizes the need for continuous surveillance for disease burden using multiple diagnostic tests and also warrants the need for an appropriate molecular diagnostic for early detection of chikungunya virus

Impaired platelet-dependent thrombin generation associated with thrombocytopenia is improved by prothrombin complex concentrates in vitro.

BACKGROUND: Impaired thrombin generation (TG) in patients with acquired coagulopathy, is due to low coagulation factors and thrombocytopenia. The latter is typically treated with platelet transfusions and the former with plasma and occasionally with prothrombin complex concentrates (PCCs). We hypothesized that manipulating the concentrations of coagulation factors might result in restoration of platelet-dependent TG over and above that of simple replacement therapy. OBJECTIVE: To investigate the influence of PCCs on impaired TG secondary to thrombocytopenia. METHODS: TG was evaluated by thrombin generation assay using a thrombocytopenia model in which normal plasma samples with varying platelet counts (20-300 × 109/L) were spiked with PCCs (25%-150% increase in plasma PCC levels). RESULTS: PCCs and platelets significantly increased TG in a dose-dependent manner in vitro. Two-way repeated measures of analysis of variance showed variance in peak height, area under the curve, time to peak, and velocity. This variance explained, respectively, by levels of PCC was 47, 59, 25 and 53%; by platelet count was 45, 28, 44, and 14%; by the combination was 80, 67, 70, and 62% variance; and a combination with additional interaction was 91, 84, 76, and 68%. TG at a platelet count 40 × 109/L with an approximate 25% increase in PCC concentration was similar to TG at 150 × 109/L. Similarly, patient samples spiked ex vivo with PCCs also showed highly significant improvements in TG. CONCLUSIONS: Impaired TG of thrombocytopenia is improved by PCCs, supporting the need for additional studies in complex coagulopathies characterized by mild to moderate thrombocytopenia and abnormal coagulation

Synergistic effect of intrathecal fentanyl and bupivacaine in spinal anesthesia for cesarean section

BACKGROUND: Potentiating the effect of intrathecal local anesthetics by addition of intrathecal opiods for intra-abdominal surgeries is known. In this study by addition of fentanyl we tried to minimize the dose of bupivacaine, thereby reducing the side effects caused by higher doses of intrathecal bupivacaine in cesarean section. METHODS: Study was performed on 120 cesarean section parturients divided into six groups, identified as B(8), B(10 )and B (12.5 )8.10 and 12.5 mg of bupivacaine mg and FB(8), FB(10 )and FB (12.5 )received a combination of 12.5 μg intrathecal fentanyl respectively. The parameters taken into consideration were visceral pain, hemodynamic stability, intraoperative sedation, intraoperative and postoperative shivering, and postoperative pain. RESULTS: Onset of sensory block to T6 occurred faster with increasing bupivacaine doses in bupivacaine only groups and bupivacaine -fentanyl combination groups. Alone lower concentrations of bupivacaine could not complete removed the visceral pain. Blood pressure declined with the increasing concentration of Bupivacaine and Fentanyl. Incidence of nausea and shivering reduces significantly whereas, the postoperative pain relief and hemodynamics increased by adding fentanyl. Pruritis, maternal respiratory depression and changes in Apgar score of babies do not occur with fentanyl. CONCLUSION: Spinal anesthesia among the neuraxial blocks in obstetric patients needs strict dose calculations because minimal dose changes, complications and side effects arise, providing impetus for this study. Here the synergistic, potentiating effect of fentanyl (an opiod) on bupivacaine (a local anesthetic) in spinal anesthesia for cesarian section is presented, fentanyl is able to reduce the dose of bupivacaine and therefore its harmful effects

Mitotic phosphorylation activates hepatoma-derived growth factor as a mitogen

<p>Abstract</p> <p>Background</p> <p>Hepatoma-derived growth factor (HDGF) is a nuclear protein that is a mitogen for a wide variety of cells. Mass spectrometry based methods have identified HDGF as a phosphoprotein without validation or a functional consequence of this post-translational modification.</p> <p>Results</p> <p>We found that HDGF in primary mouse aortic vascular smooth muscle cells (VSMC) was phosphorylated. Wild type HDGF was phosphorylated in asynchronous cells and substitution of S103, S165 and S202 to alanine each demonstrated a decrease in HDGF phosphorylation. A phospho-S103 HDGF specific antibody was developed and demonstrated mitosis-specific phosphorylation. HDGF-S103A was not mitogenic and FACS analysis demonstrated a G2/M arrest in HDGF-S103A expressing cells, whereas cells expressing HDGF-S103D showed cell cycle progression. Nocodazole arrest increased S103 phosphorylation from 1.6% to 29% (P = 0.037).</p> <p>Conclusions</p> <p>Thus, HDGF is a phosphoprotein and phosphorylation of S103 is mitosis related and required for its function as a mitogen. We speculate that cell cycle regulated phosphorylation of HDGF may play an important role in vascular cell proliferation.</p

Validation of a perioperative population factor VIII pharmacokinetic model with a large cohort of pediatric hemophilia a patients

AIMS: Population pharmacokinetic (PK) models are increasingly applied to perform individualized dosing of factor VIII (FVIII) concentrates in haemophilia A patients. To guarantee accurate performance of a population PK model in dose individualization, validation studies are of importance. However, external validation of population PK models requires independent data sets and is, therefore, seldomly performed. Therefore, this study aimed to validate a previously published population PK model for FVIII concentrates administrated perioperatively. METHODS: A previously published population PK model for FVIII concentrate during surgery was validated using independent data from 87 children with severe haemophilia A with a median (range) age of 2.6 years (0.03–15.2) and body weight of 14 kg (4–57). First, the predictive performance of the previous model was evaluated with MAP Bayesian analysis using NONMEM v7.4. Subsequently, the model parameters were (re)estimated using a combined dataset consisting of the previous modelling data and the data available for the external validation. RESULTS: The previous model underpredicted the measured FVIII levels with a median of 0.17 IU mL(−1). Combining the new, independent and original data, a dataset comprising 206 patients with a mean age of 7.8 years (0.03–77.6) and body weight of 30 kg (4–111) was obtained. Population PK modelling provided estimates for CL, V1, V2, and Q: 171 mL h(−1) 68 kg(−1), 2930 mL 68 kg(−1), 1810 mL 68 kg(−1), and 172 mL h(−1) 68 kg(−1), respectively. This model adequately described all collected FVIII levels, with a slight median overprediction of 0.02 IU mL(−1). CONCLUSIONS: This study emphasizes the importance of external validation of population PK models using real‐life data

A Novel, Enriched Population Pharmacokinetic Model for Recombinant Factor VIII-Fc Fusion Protein Concentrate in Hemophilia A Patients

Background The currently published population pharmacokinetic (PK) models used for PK-guided dosing in hemophilia patients are based on clinical trial data and usually not externally validated in clinical practice. The aim of this study was to validate a published model for recombinant factor VIII-Fc fusion protein (rFVIII-Fc) concentrate and to develop an enriched model using independently collected clinical data if required. Methods Clinical data from hemophilia A patients treated with rFVIII-Fc concentrate (Elocta) participating in the United Kingdom Extended Half-Life Outcomes Registry were collected. The predictive performance of the published model was assessed using mean percentage error (bias) and mean absolute percentage error (inaccuracy). An extended population PK model was developed using nonlinear mixed-effects modeling (NONMEM). Results A total of 43 hemophilia A patients (FVIII Conclusion We concluded that the existing rFVIII-Fc population PK model is valid for patients >= 12 years. However, it is not reliable in younger patients. Our alternative model, constructed from real world patient data including children, allows for better description of patients >= 5 years