Phytomedicines to Target Hepatitis B Virus DNA Replication: Current Limitations and Future Approaches.

Hepatitis B virus infection (HBV) is one of the most common causes of hepatitis, and may lead to cirrhosis or hepatocellular carcinoma. According to the World Health Organization (WHO), approximately 296 million people worldwide are carriers of the hepatitis B virus. Various nucleos(t)ide analogs, which specifically suppress viral replication, are the main treatment agents for HBV infection. However, the development of drug-resistant HBV strains due to viral genomic mutations in genes encoding the polymerase protein is a major obstacle to HBV treatment. In addition, adverse effects can occur in patients treated with nucleos(t)ide analogs. Thus, alternative anti-HBV drugs of plant origin are being investigated as they exhibit excellent safety profiles and have few or no side effects. In this study, phytomedicines/phytochemicals exerting significant inhibitory effects on HBV by interfering with its replication were reviewed based on different compound groups. In addition, the chemical structures of these compounds were developed. This will facilitate their commercial synthesis and further investigation of the molecular mechanisms underlying their effects. The limitations of compounds previously screened for their anti-HBV effect, as well as future approaches to anti-HBV research, have also been discussed.

Guidelines and controversies in the management of diabetic ketoacidosis - A mini-review.

Diabetic ketoacidosis (DKA) is a complication seen in patients with both type 1 and type 2 diabetes. Due to its large, growing economic impact with associated morbidity, closer look at proper management is important. Factors involved in appropriate management involves fluid resuscitation, insulin regimen, and electrolyte replacement including types of fluid and insulin treatment. The caveat with generalized protocol is application to special populations such as renal or heart failure patients the sequelae of complications due to pathophysiology of the disease processes. This leads to complications and longer length of stay in the hospital, therefore, possibly increased cost and resource utilization during the hospitalization. This review takes a closer look at current guidelines of DKA management and resource utilization, the drawbacks of current management protocols and the cost associated with it. Therefore, a need for amendment to existing protocol or initiation of a newer guideline that properly manages DKA should incorporate special populations and appropriate regimen of fluid resuscitation, insulin therapy and electrolyte management.

Bovine carotid artery biologic graft outperforms expanded polytetrafluoroethylene for hemodialysis access.

OBJECTIVE: Arteriovenous grafts remain reliable substitutes for permanent hemodialysis access in patients without a suitable autogenous conduit. Advances in conduit design and endovascular management of access-related complications question the preference for synthetic conduits over biologic grafts in contemporary practice. In this study, we compared outcomes between a bovine carotid artery (BCA) biologic graft and expanded polytetrafluoroethylene (ePTFE) grafts for hemodialysis access in a recent cohort of patients. METHODS: This was a single-institution retrospective review of 120 consecutive grafts placed in 98 patients between January 1, 2011, and June 30, 2014. Univariate methods (χ2, analysis of variance, t-test) were used to compare demographic and medical characteristics of patients who received each graft type. Kaplan-Meier, log-rank tests, univariate and multivariate logistic analyses, and Cox regression analyses were used to evaluate patency and graft complications. Outcomes were defined and analyzed according to reporting guidelines published by the Society for Vascular Surgery. RESULTS: Of the 120 grafts studied, 52 (43%) were BCA and 68 (57%) were ePTFE. Successful graft use for dialysis was 96% (95% confidence interval [CI], 90%-100%) for BCA and 84% (95% CI, 74%-93%) for ePTFE (P = .055). Comparing BCA vs ePTFE, estimates for primary patency were 30% vs 43% at 1 year and 16% vs 29% at 2 years (P = .27). Primary assisted patency was 36% vs 45% at 1 year and 24% vs 35% at 2 years (P = .57). Secondary patency was 67% vs 48% at 1 year and 67% vs 38% at 2 years (P = .05). There were no differences in primary (hazard ratio [HR], 0.70; 95% CI, 0.40-1.28; P = .25) and primary assisted (HR, 0.87; 95% CI, 0.46-1.65; P = .67) patency for BCA compared with ePTFE. However, secondary patency was higher for BCA compared with ePTFE (HR, 2.92; 95% CI, 1.29-6.61; P = .01). Graft infection rates during the study period were 15.4% for BCA and 20.6% for ePTFE (P = .47). The significant predictors of graft failure were higher body mass index (HR, 1.06; 95% CI, 1.00-1.11; P = .04) and hyperlipidemia (HR, 2.94; 95% CI, 1.27-6.76; P = .01). CONCLUSIONS: In this study of a recent cohort of patients who received arteriovenous grafts, primary and primary assisted patencies were similar between BCA and ePTFE grafts. However, secondary patency was higher for BCA, indicating better durability for the biologic graft than for ePTFE grafts in patients whose anatomy preclude placement of an arteriovenous fistula.

Intrinsic excitability of CA1 pyramidal neurones from the rat dorsal and ventral hippocampus.

The hippocampus has a central role in learning and memory. Although once considered a relatively homogenous structure along the longitudinal axis, it has become clear that the rodent hippocampus can be anatomically and functionally divided into a dorsal component generally associated with spatial navigation, and a ventral component primarily associated with non-spatial functions that involve an emotional component. The ventral hippocampus (VHC) is also more sensitive to epileptogenic stimuli than the dorsal hippocampus (DHC), and seizures tend to originate in the VHC before spreading to other brain regions. Although synaptic and biochemical differences in DHC and VHC have been investigated, the intrinsic excitability of individual neurones from the DHC and VHC has received surprisingly little attention. In this study, we have characterized the intrinsic electrophysiological properties of CA1 pyramidal neurones from the DHC and the VHC using the whole-cell current-clamp method. Our results demonstrate that somatic current injections of equal magnitude elicit significantly more action potentials in VHC neurones than DHC neurones, and that this difference stems from the more depolarized resting membrane potential (RMP; 7 mV) and higher input resistance (R(in); 46 M measured from RMP) observed in VHC neurones. These differences in RMP and R(in) were also observed in dendritic whole-cell current-clamp recordings. Furthermore, morphological reconstructions of individual neurones revealed significant differences in the dendritic branching pattern between DHC and VHC neurones that could, in principle, contribute to the lower somatic R(in) of DHC neurones. Together, our results highlight significant differences in the intrinsic electrophysiological properties of CA1 pyramidal neurones across the longitudinal hippocampal axis, and suggest that VHC neurones are intrinsically more excitable than DHC neurones. This difference is likely to predispose the VHC to hyperexcitability.