Molecular Approach for Distal Renal Tubular Acidosis Associated AE1 Mutations

The molecular approaches to distal renal tubular acidosis (dRTA) associated AE1 mutations lead us to understand the genetic and pathophysiological aspects of the acidification defects. An unanticipated high value of the urine-blood (U-B) PCO2 after NaHCO3 loading observed in a case of dRTA and southeast Asian ovalocytosis (SAO) might be from a mistarget of the AE1 to the luminal membrane of type A intercalated cells. The mutations of the AE1 gene resulted in SAO and also affected renal acidification function. Notwithstanding, after the NH4Cl loading in 20 individuals with SAO, the acidification in the distal nephron was normal. The presence of both SAO and G701D mutations of AE1 gene would explain the abnormal urinary acidification in the patients with the compound heterozogosity. In terms of the effect of the mutations on trafficking of AE1, truncated kidney isoform (kAE1) of wild-type showed a 'dominant-positive effect' in rescuing the recessive mutant kAE1 (S773P or G701D) trafficking to the plasma membrane, in contrast with the dominant mutant kAE1 (R589H) resulting in a 'dominant-negative effect' when heterodimerized with the wild-type kAE1. It is notable that the dominant mutants kAE1 (R901X or G609R) expression in MDCK cells clearly results in aberrant surface expression with some mutant protein appearing at the apical membrane. These might result in net bicarbonate secretion and increasing U-B PCO2 in the distal nephron. The molecular physiological and genetic approaches have permitted identification of the molecular defects, predominantly in transporter proteins, and should in turn prompt development of novel therapeutic strategies

Effectiveness of Ayurved Siriraj Prasa-Nam-Nom Recipe on Breast Milk Volume in Early Postpartum Women: A Randomized, Double-Blind, Placebo- Controlled Trial

Objective: To explore the effectiveness of Ayurved Siriraj Prasa-Nam-Nom (ASPNN) recipe on breast milk production in early postpartum women. Methods: Fifty-four normal vaginal term delivery mothers who had inadequate milk volume were enrolled into this randomized, double-blind, placebo-controlled trial. All participants received ASPNN or placebo 1,500 mg three times/day for 3 days in the hospital and 7 days at home. Primary outcomes, including breast milk volume, %creamatocrit, and level of prolactin, were evaluated on day 1 and day 3. Satisfaction scores, adverse effects, and types of breastfeeding were also determined. Results: On day 3, milk volume was increased in both groups. The median volume of ASPNN group was 19 ml, while that of the placebo group was 30 ml. The median %creamatocrit of ASPNN and placebo group were 7.17% and 6.98%, respectively. Mean serum prolactin levels of ASPNN and placebo group were 321.76 + 114.23 ng/ml and 323.78 + 116.68 ng/ml, respectively. Although the effects were not difference from the placebo, the reduction of prolactin in ASPNN was lower. Minor adverse effects included skin rash and mild diarrhea. Exclusive breastfeeding rate on day 11 in ASPNN and placebo group were 92.6 % and 88.5%, respectively. Conclusion: Short term ASPNN supplementation produce no direct effect on breast milk volume, creamatocrit, and serum prolactin. It was safe and might help maintaining serum prolactin. A future trial with more participants and longer period should be conducted to confirm the effect of ASPNN on breast milk quantity and quality

History, epidemiology and regional diversities of urolithiasis

Archeological findings give profound evidence that humans have suffered from kidney and bladder stones for centuries. Bladder stones were more prevalent during older ages, but kidney stones became more prevalent during the past 100 years, at least in the more developed countries. Also, treatment options and conservative measures, as well as ‘surgical’ interventions have also been known for a long time. Our current preventive measures are definitively comparable to those of our predecessors. Stone removal, first lithotomy for bladder stones, followed by transurethral methods, was definitively painful and had severe side effects. Then, as now, the incidence of urolithiasis in a given population was dependent on the geographic area, racial distribution, socio-economic status and dietary habits. Changes in the latter factors during the past decades have affected the incidence and also the site and chemical composition of calculi, with calcium oxalate stones being now the most prevalent. Major differences in frequency of other constituents, particularly uric acid and struvite, reflect eating habits and infection risk factors specific to certain populations. Extensive epidemiological observations have emphasized the importance of nutritional factors in the pathogenesis of urolithiasis, and specific dietary advice is, nowadays, often the most appropriate for prevention and treatment of urolithiasis

STABILITY OF PHYLLANTHUS EMBLICA EXTRACT IN LIPOSOMES

Phyllanthus emblica L. (P. emblica) has many benefits in its biological effects, including anti-oxidant activity, anti-tyrosinase activity, anti-microbial activity and protection against radiation-induced chromosome damage. However, the stability is a major concern of the P. emblica extract. Therefore, the objective of this research is to compare the stability of the P. emblica extract in liposomes and buffer solutions at pH 5.5 and 7.4. The lipid compositions of liposomal membranes were egg phophatidylcholine (Lipoid E80) and cholesterol at 2:1 molar ratio with cholesterol ester as a stabilizer. The concentrations of P. emblica extract were varied at 1, 2, 3, 4 and 5 mg/mL. The encapsulation efficiency and chemical stability were determined by measuring the amount of total phenolic compounds using UV-VIS spectrophotometer. The highest percent encapsulation efficiency was found at 52.83% obtained from liposome formulation containing 1 mg/mL of P. emblica extract prepared at pH 5.5. In addition, the above preparation was stable at least 12 weeks when stored in a refrigerator at 4°C. The particle size of the liposomes stored for 0 and 12 weeks was not significantly different with the mean particle sizes of 5.790 + 0.756 and 5.553 + 0.647 µm respectively. Summarily, P. emblica extract in liposomes is more stable than that in buffer solutions

The COVID-19 pandemic: the effect on airway Management in non-COVID emergency patients

BACKGROUND: During the COVID-19 outbreak, healthcare providers might have avoided droplet/aerosol-generating procedures, such as non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) due to the concern of themselves being infected. We hypothesized that this change of practice could have also occurred to other non-COVID-infected patients in the Emergency Department (ED). METHODS: A retrospective analytic study was conducted in the ED of Siriraj Hospital, Bangkok, Thailand, including adult patients presenting with signs and symptoms of respiratory distress between 1 March and 30 April 2020 (the COVID period). A comparison group using the same inclusion criteria was retrieved from 1 March to 30 April 2019 (the pre-COVID period). The primary outcome was rate of NIV and HFNC use. The secondary outcomes were rate of intubation, failure of NIV and HFNC, complications, and mortality. RESULTS: A total of 360 and 333 patients were included during the pre-COVID and COVID periods, respectively. After adjusting for baseline differences, patients in the COVID period were less likely to receive either NIV or HFNC than the pre-COVID period (adjusted OR 0.52 [95%CI 0.29–0.92]). Overall, intubation rate was similar between the two study periods. However, patients in respiratory distress with pulmonary edema had a relatively higher intubation rate in the COVID period. There were higher failure rates of NIV and HFNC, more infectious complications, and a higher rate of mortality in the pre-COVID period. CONCLUSION: During the COVID-19 pandemic, the overall usage of NIV and HFNC in emergency non-COVID patients decreased. Although not affecting the overall intubation rate, this change of practice could have affected some groups of patients. Therefore, treatment decisions based on a balance between the benefits to the patients and the safety of healthcare providers should be made

The COVID-19 pandemic: the effect on airway Management in non-COVID emergency patients

Abstract Background During the COVID-19 outbreak, healthcare providers might have avoided droplet/aerosol-generating procedures, such as non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) due to the concern of themselves being infected. We hypothesized that this change of practice could have also occurred to other non-COVID-infected patients in the Emergency Department (ED). Methods A retrospective analytic study was conducted in the ED of Siriraj Hospital, Bangkok, Thailand, including adult patients presenting with signs and symptoms of respiratory distress between 1 March and 30 April 2020 (the COVID period). A comparison group using the same inclusion criteria was retrieved from 1 March to 30 April 2019 (the pre-COVID period). The primary outcome was rate of NIV and HFNC use. The secondary outcomes were rate of intubation, failure of NIV and HFNC, complications, and mortality. Results A total of 360 and 333 patients were included during the pre-COVID and COVID periods, respectively. After adjusting for baseline differences, patients in the COVID period were less likely to receive either NIV or HFNC than the pre-COVID period (adjusted OR 0.52 [95%CI 0.29–0.92]). Overall, intubation rate was similar between the two study periods. However, patients in respiratory distress with pulmonary edema had a relatively higher intubation rate in the COVID period. There were higher failure rates of NIV and HFNC, more infectious complications, and a higher rate of mortality in the pre-COVID period. Conclusion During the COVID-19 pandemic, the overall usage of NIV and HFNC in emergency non-COVID patients decreased. Although not affecting the overall intubation rate, this change of practice could have affected some groups of patients. Therefore, treatment decisions based on a balance between the benefits to the patients and the safety of healthcare providers should be made. </jats:sec

Emblica extract prevents cisplatin-induced apoptosis in dermal papilla fibroblasts

Cisplatin is a widely prescribed anticancer agent that causes hair loss in patients. Since the dermal papilla (DP) fibroblasts are known to be a key mediator in controlling hair growth and loss, understanding the effect and underlying mechanism of cisplatin on these cells may lead to new strategy for hair loss protection in chemotherapy patients. Less is known regarding the effect of cisplatin on DP fibroblasts. We thus treated DP cells with cisplatin (0-250 mmol/L) and found that cisplatin induced DP cell death in a concentration-dependent manner. Our results showed that the mode of cisplatin-induced DP cell death was mainly through apoptosis mechanism. Our results also indicated that the intracellular reactive oxygen species (ROS) induction caused by cisplatin treatment was associated with DP cell apoptosis and cisplatin-induced apoptosiscould be attenuated by addition of antioxidant N-acetylcysteine (1 mmol/L) and glutathione (5 mmol/L). Moreover, subtoxicconcentrations (0-500 mg/mL) of Phyllanthus emblica Linn (emblica) extracts, a known natural antioxidant, showed a strong inhibition effect on cisplatin-induced intracellular ROS induction and subsequently protected DP cells from cisplatin-induced apoptosis

Regional discrimination of change in runoff

Bibliography: pages 39-40