Differential involvement of L- and T-type Ca2+ channels, store-operated calcium channel (TRPC) and Rho-kinase signaling pathway(s) in PGF2α-induced contractions in myometrium of non-pregnant and pregnant buffaloes (Bubalus bubalis)

Publication date: Available online 12 September 2017
Source:Prostaglandins & Other Lipid Mediators
Author(s): Abhishek Sharma, Udayraj P. Nakade, Pooja Jaitley, Vipin Sharma, Soumen Choudhury, Satish Kumar Garg
This study unravels the differential involvement of calcium signaling pathway(s) in PGF2α-induced contractions in myometrium of non-pregnant and pregnant buffaloes. Compared to the myometrium of pregnant animals, myometrium of non-pregnant buffaloes was more sensitive to PGF2α–induced contractile effect as manifested by the changes in mean integral tension (MIT) and tonicity. However, phasic contraction was significantly more in myometrium of pregnant animals. The uterotonic effect of PGF2α was dependent on extracellular Ca²⁺ and its influx through nifedipine-sensitive L-type Ca²⁺ channels both in non-pregnant and pregnant animals, but T-type Ca²⁺ channels play an additional role during pregnancy. Entry of extracellular Ca²⁺ is triggered by enhanced functional involvement of Pyr3-sensitive TRPC3 channels and Rho-kinase pathways to regulate uterotonic action of PGF2α in myometrium of non-pregnant buffaloes while these are down-regulated during pregnancy as there was significantly reduced expression of Rho-A proteins in myometrium of pregnant buffaloes and down-regulation of these facilitate uterine quiescence. Intracellular Ca²⁺ plays minor role in myometrium of both the non-pregnant and pregnant buffaloes.

Graphical abstract

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2fhpjfn

Natriuretic peptides in the control of lipid metabolism and insulin sensitivity

Summary

Natriuretic peptides have long been known for their cardiovascular function. However, a growing body of evidence emphasizes the role of natriuretic peptides in human substrate and energy metabolism, thereby connecting the heart with several insulin-sensitive organs like adipose tissue, skeletal muscle and liver. Obesity may be associated with an impaired regulation of the natriuretic peptide system, also indicated as a natriuretic handicap. Evidence points towards a contribution of this natriuretic handicap to the development of obesity, type 2 diabetes mellitus and cardiometabolic complications, although the causal relationship is not fully understood. Nevertheless, targeting the natriuretic peptide pathway may improve metabolic health in obesity and type 2 diabetes mellitus. This review will focus on current literature regarding the metabolic roles of natriuretic peptides with emphasis on lipid metabolism and insulin sensitivity. Furthermore, it will be discussed how exercise and lifestyle intervention may modulate the natriuretic peptide-related metabolic effects.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2xxea4U

AICAR Administration Attenuates Hemorrhagic Hyperglycemia and Lowers Oxygen Debt in Anesthetized Male Rabbits

Yi Huang, Paul H. Ratz, Amy S. Miner, Victoria A. Locke, Grace Chen, Yang Chen, Robert W. Barbee

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Molecular Mechanisms Underlying Renin-Angiotensin-Aldosterone System Mediated Regulation of BK Channels

Zhen-Ye Zhang, Ling-Ling Qian, Ru-Xing Wang

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Reflected vision in surgical practice – A novel method to circumvent posture related Musculo-skeletal disorders

Musclulo-skeletal disorders (MSD) rank very high among the occupational hazards that plague dentists including oral and maxillofacial surgeons. This has been attributed to abnormal posture while operating, with the severity being directly proportional to the duration of procedures. The prevalence of neck & back pain is found to be as high as 81% among practicing dentists 1. A questionnaire based study involving 5305 practising oral & maxillofacial surgeons in the United States of America revealed that 45% of the surgeons had undergone treatment for MSD, with 8% needing a surgical intervention.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2y4bJUm

Enzalutamide-warfarin interaction necessitating warfarin dosage adjustment: A case report of successful clinical management

Summary

What is known and objectives

Enzalutamide package labeling recommends avoiding concurrent warfarin use due to potential reductions in warfarin concentrations via enzalutamide-associated hepatic enzyme induction. A case of successful management of this interaction via warfarin adjustments is reported.

Case description

A 77-year-old Caucasian male, previously relatively stable on warfarin 42-45 mg weekly, reported to clinic after the recent start of enzalutamide and subsequent hospitalization with a subtherapeutic International Normalized Ratio (INR). A 50% increase in weekly warfarin dose resulted in a therapeutic INR. Enzalutamide was temporarily discontinued, and a 33% weekly warfarin dose decrease resulted in two therapeutic INRs.

What is new and conclusion

This is the first case to highlight the clinical significance of this interaction, noting that patients taking enzalutamide may require approximately 30%-50% adjustment in their warfarin dosage to maintain a therapeutic INR.

Enzalutamide is a moderate CYP2C9 inducer, which can reduce the plasma concentrations of warfarin via metabolism induction when given concurrently. Although not always clinically feasible, enzalutamide package labeling recommends to avoid this combination due to the narrow therapeutic index of warfarin and the risk of significant INR fluctuations. Our case illustrates that patients receiving this combination can be successfully managed in clinical practice and may require warfarin dosage adjustments of 30-50% to maintain a therapeutic INR.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2x06THU

Lymph node-positive prostate cancer after robotic prostatectomy and extended pelvic lymphadenectomy

Abstract

Optimal management of node-positive prostate cancer patients after prostatectomy remains a challenge. We evaluated clinically localized patients who demonstrated node positivity and identified predictors for secondary treatment. From 2010 to 2015, clinically localized prostate cancer patients who underwent robot prostatectomy with extended lymphadenectomy and node-positive disease on pathologic analysis were identified. Clinical N1, M1 or salvage cases were excluded. Patients were stratified based on secondary treatments. Kaplan–Meier method was used to determine the time to biochemical and metastatic recurrence. Multivariate logistic regression was used to identify predictors for additional treatment. 145 patients (45 no additional therapy, 47 adjuvant, 53 salvage) had a median follow-up of 31.2 months. Salvage patients had higher median pre-operative prostate-specific antigen (10.8 vs. 9.7 vs. 8.2, p = 0.1), higher percentage of pathologic Gleason ≥8 (50.9 vs. 38.3% and 22.2%, p < 0.01), and higher median-positive nodes (3 vs. 1 and 1, p < 0.0001) compared to adjuvant and no treatment groups, respectively. Pathologic Gleason ≥8 (OR = 3.5, p = 0.007) and positive nodes ≥2 (OR = 3.3, p = 0.006) were associated with additional therapy. In the no treatment group, two-year estimated BCRFS was 74.3%. Two-year metastatic recurrence-free rates for no treatment, adjuvant and salvage groups were 100, 87.5, and 80.9%, respectively (p = 0.01). Observation is a viable alternative for low metastatic burden patients. In the largest series of node-positive patients from robotic prostatectomy and extended lymphadenectomy, those with pathologic Gleason ≥8 and positive lymph nodes ≥2 were more likely to receive additional treatment.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2wVLcev