Negative inotropic mechanisms of β-cardiotoxin in cardiomyocytes by depression of myofilament ATPase activity without activation of the classical β-adrenergic pathway

Beta-cardiotoxin (β-CTX) from the king cobra venom (Ophiophagus hannah) was previously proposed as a novel β-adrenergic blocker. However, the involvement of β-adrenergic signaling by this compound has never been elucidated. The objectives of this study were to investigate the underlying mechanisms of β-CTX as a β-blocker and its association with the β-adrenergic pathway. The effects of β-CTX on isolated cardiac myocyte functions, calcium homeostasis, the phosphorylation level of targeted proteins, and the myofibrillar ATPase activity were studied. Healthy Sprague Dawley rats were used for cardiomyocytes isolation. Like propranolol, β-CTX attenuated the cardiomyocyte inotropy and calcium transient alterations as induced by isoproterenol stimulation. In contrast, these effects were not observed in forskolin-treated cells. Interestingly, cardiomyocytes treated with β-CTX showed no changes in phosphorylation level at any PKA-targeted sites in the myofilaments as demonstrated in Western blot analysis. The skinned fibers study revealed no change in myofilament kinetics by β-CTX. However, this protein exhibited the direct inhibition of myofibrillar ATPase activity with calcium de-sensitization of the enzyme. In summary, the negative inotropic mechanism of β-CTX was discovered. β-CTX exhibits an atypical β-blocker mechanism. These properties of β-CTX may benefit in developing a novel agent aid to treat hypertrophic cardiomyopathy.

A Prospective Study on Evaluation of Efficacy of Combination Therapy of Tamsulosin and Deflazacort In Ureteric Stone Expulsion

The patients with ureteric stone are increasing day by day all over the world. A ureteric stone is a mineral mass in the ureter which may or may not originated in the kidney and travelled down to the ureter. The presence of stone in ureter causes inflammation and edema. There are mainly four types of ureteric stone such as Calcium stones, Uric acid stones, Struvite stone, Cystine stone. About 23-53% of spontaneous stone expulsion occurs where the size of stone is 5-10mm diameter. Tamsulosin is an alpha 1 adrenergic blocker which has a spasmolytic action and thus hasten stone expulsion. Deflazacort is a corticosteroid prodrug which acts on the glucocorticoid receptor to show an anti-inflammatory effect. Deflazacort decreases the edema and when prescribed along with alpha 1 adrenergic receptor blocker it facilitate the expulsion of calculi. This study was conducted in 20 patients diagnosed with ureteric calculi. The study was conducted by using suitable proforma for collecting various data’s like site of stones, presence of hydronephrosis, signs and symptoms. Health related quality of life of the patients with ureteric calculi under the treatment of Tamsulosin and Deflazacort combination were assessed by using Wisconsin Stone-QOL questionnaire. As counselling aid patients information leaflet was provided. The patients were asked to review after 10 days of taking the medication. At the end of the study all the parameters and scores were compared with baseline to the end of the study. In our study we analyzed that the data collected from 20 patients diagnosed with ureteric calculi accessed the improvement of quality of life of patients under the treatment of Tamsulosin and Deflazacort combination by using Wisconsin Stone-QOL questionnaire. The observed difference before and after the treatment with Tamsulosin and Deflazacort w

Development and Evaluation of Micro Emulsion Formulations of Nebivolol for Solubility Enhancement

Nebivolol HCl is a newer drug of β1-adrenergic blocker category, basically used as anti-hypertensive. It is a 3rd generation, antagonist, having NO (nitric oxide) enhancing vasodilator properties. It has 12% oral bioavailability, because of its pre systemic metabolism by the means of cytochrome P450 2D6 enzymes. Its log P value is 4.03 and 5mg is its daily dose. It is highly lipophilic drug and belongs to class BCS II, with slow dissolution. Bioavailability of any drug can be improved by avoiding its first pass metabolism and promoting solubility. Several researchers have worked on the development of ME formulations on different poor water-soluble drugs, to increase their solubility. The purpose of this study is an attempt to enhance the solubility to improve the bioavailability of nebivolol drug by developing a novel delivery system that is microemulsion (ME) .ME formulations were developed using different oil, surfactant and co-surfactants in different ratio and studied on various parameters. Different preformulation tests done on received sample of Nebivolol. FTIR study was performed in order to find out any interactions between the ingredients. Based on the solubility Capmul Pg-12 was finalized oil, Tween 80 as surfactant, propylene glycol as the cosurfactant based on solubility and emulsification efficiency. Five Nebivolol ME formulations were successfully developed by use of oil, water, SA and Co-SA different ratio. Prepared formulations were studied for different properties- transmittance (%), pH, refractive index, viscosity, drug content, and solubility. It was seen that after 4 hours of diffusion, the drug released from the formulation ME5 is faster and more than that of the other i.e., 90.2±0.06%. It was found that ME5 was more stable and Soluble than other prepared formulations. With the better solubilty the bioavailability of Nebivolol will increased and helps in faster absorption and High diffusion in systemic circulation with lower or no risk of degradation. It somehow also reduced frequent intake of drug. Keywords: Nebivolol, micro emulsion, Ternary phase diagram, surfactant, co-surfactant.

Anaesthetic Management for Laparascopic Adrenalectomy for Pheochromocytoma as Part of Vonn Hippel-Lindau Syndrome in Child

Pheochromocytoma is a tumor that originates from either chromaffincells in adrenal medulla or in other paraganglia tissues (paragangliomas) of the sympathetic nervous system. It might be familial and associated with hereditary tumors such as Von Hippel-Lindau syndrome and multiple endocrine neoplasia type II. The symptoms are variable related to the level of secreted catecholamine. The most common are hypertension, tachycardia, headache and abdominal pain. The most effective treatment is surgical resection as in recent years, laparoscopic surgery has been more preferred. The perioperative management is quite challenging especially in view of hemodynamic fluctuations. Although there is a considerable amount of information on the management of the adult with phaeochromocytoma, much less has been written concerning children with the disease. We present a case of 9-year-old hypertensive boy with left sided pheochromocytoma, scheduled for excision of tumour. He had presented with complaints of pain in abdomen, excessive sweating, headache and raised blood pressure, as well as family anamnesis for von Hippel-Lindau syndrome (father with confirmed diagnosis). Diagnosis was confirmed by CT scan (abdomen), raised 24-hour urinary catecholamine levels and genetics tests. Preoperative blood pressure was controlled with prazosin (ά-adrenergic blocker). The anaesthetic technique used was general anaesthesia. Child was later discharged on oral antihypertensive.

Cardioluminescence in transgenic zebrafish embryos: a calcium imaging tool to study drug effects and pathological modeling

The zebrafish embryo has emerged as an excellent model in cardiovascular research. The existing techniques to monitor Ca2+ in the heart based on fluorescent Ca2+ biosensors are limited due to phototoxicity and photobleaching. To overcome these issues, we have used bioluminescence. We generated a transgenic line expressing GFP-Aequorin in the heart, Tg(cmlc2:GA), and optimized an in vivo aequorin reconstitution protocol to improve the luminescence capacity. This allowed imaging Ca2+ in long duration recordings in embryos of 3 to 5 days post-fertilization. The analogs diacetyl h-coelenterazine and f-coelenterazine enhanced the light output and signal-to-noise ratio from the embryos. With this cardioluminescence model, we monitored the time-averaged Ca2+ levels and beat-to-beat Ca2+ oscillations. Changes in Ca2+ levels were observed by incubation with BayK8644, an L-type Ca2+ channel agonist, the channel blocker nifedipine, and β-adrenergic blocker propranolol. Treatment of zebrafish embryos with terfenadine for 24 hours has been proposed as a model of heart failure. Tg(cmlc2:GA) embryos treated with terfenadine showed a 2:1 atrioventricular block and a decrease in the ventricular Ca2+ levels.

Doxazosin Effect on Neurogenic Bladder with Urine Retention in Female Dogs

This short communication describes the effect of Doxazosin in case of urinary retention in female dogs due to motor neuron lesions produced by spinal trauma or spinal compression consecutively to intervertebral disk degeneration and extrusion. The study aims to determine whether the treatment of urinary retention in case of neurogenic bladder in female dogs, using 1 adrenergic blocker is effective in spontaneous recovery of the examined patients. Ten female dogs presenting with urinary retention were examined in the laboratory of Radiology, Faculty of Veterinary Medicine Cluj Napoca. The patients were examined using CT, radiography and ultrasonography in order to identify the spinal cord injury that is responsible for neurogenic bladder. The dose of Doxazosin used in treatment of voiding problem in neurogenic bladder was 1mg/kg, single dose per day. Depending on the spinal cord compression cause, the urine retention symptom was resolved.

Evaluation of static and dynamic Pupillometry changes in men using Silodosin for benign prostatic hypertrophy

Background Intraoperative floppy iris syndrome is a variant of the small pupil syndrome that has been observed during cataract surgery in some patients currently or previously treated with α1 adrenergic blockers. It is important for cataract surgeons to predict the probable complications preoperatively. Our study aims to evaluate the static and dynamic pupil characteristics of patients treated with silodosin—a selective α1 adrenergic blocker—for benign prostate hypertrophy (BPH) and to compare these values with healthy subjects using an automatic quantitative pupillometry system. Methods A total of 74 BPH patients treated with silodosin for six months (group 1) and 30 healthy subjects (group 2) were enrolled in this prospective multidisciplinary cross-sectional study. Static and dynamic pupillometric measurements were obtained under optimized conditions, and the results were compared between the two groups. Results Seventy-four male patients with a mean age of 63,35 ± 7,21 (46–77) years with BPH treated with silodosin and 30 normal male subjects with a mean age of 63,07 ± 4,73 (52–71) years were analyzed. There were statistically significant differences between the groups with regard to scotopic pupil diameter (PD), high photopic PD, and low photopic PD (p < 0.001, for each one). The patient group had statistically significant higher values of amplitude and velocity of pupil contraction and lower values of duration of pupil contraction and latency as well as duration and velocity of pupil dilation. Conclusion The static and dynamic pupil characteristics of subjects treated with silodosin for BPH are different from those of healthy eyes. In addition, our results may have shed light on the risk for intraoperative floppy iris syndrome (IFIS) before cataract surgery; thus, surgeons can be alert and take precautions.

A COMPARATIVE STUDY OF USE OF TAMSULOSIN IN PREVENTION OF POSTOPERATIVE URINARY RETENTION IN PATIENTS OPERATED UNDER SPINAL ANAESTHESIA

INTRODUCTION -Urinary retention is one of the most common complications of surgical procedures done under spinal anaesthesia. Postoperative urinary retention (POUR) is a common and potentially serious morbidity. Overall incidence of POUR ranges from 5% to 70%. AIMS AND OBJECTIVES - The aim of this prospective study was to investigate the prophylactic effect of Tamsulosin, a super-selective α-1a adrenergic blocking agent, on the development of urinary retention in patients undergoing elective surgeries under spinal anaesthesia METHOD- This is a randomized control trial done in patients undergoing elective surgery under spinal anaesthesia during this study period of one and half years by taking 80 patients each in Tamsulosin group and control group RESULTS- There was signicantly lower in POUR in Tamsulosin group compared to placebo, independent of the PVR, Prostate size in USG in cc, Pre op uid administered in ml and duration of surgery. CONCLUSION- Prophylactic use of alpha-adrenergic blocker is effective in preventing postoperative urinary retention thereby avoiding the morbidity associated with bladder catheterisation.

Static And Dynamic Pupillometric Changes With Silodosin; Selective α1 Adrenoceptor Blocker

Backround: Intraoperative floopy iris syndrome is a variant of the small pupil syndrome that has been observed during cataract surgery in some patients currently or previously treated with the α1 adrenergic blockers. It is important for cataract surgeons to predict the probable complications, preoperatively. The aim of our study is to evaluate the static and dynamic pupil characteristics of patients treated with silodosin –a selective α1 adrenergic blocker- for Benign Prostate Hypertrophy (BPH) and to compare these values with healthy subjects using an automatic quantitative pupillometry system.Methods: A total of 74 BPH patients treated with silodosin for six months (group 1) and 30 healthy subjects (group 2) were enrolled in this prospective multidisciplinary cross-sectional study. Static and dynamic pupillometric measurements were obtained under optimized conditions and the results were compared between the two groups.Results: Seventy four male patients with a mean age of 63,35±7,21 (46-77) years with BPH treated with silodosin and 30 normal male subjects with a mean age of 63,07±4,73 (52-71) years were analyzed. There were statistically significant differences between the groups with regard to scotopic pupil diameter (PD), high photopic PD, and low photopic PD (p<0.001, for each one). Patient group has statistically significant higher values of amplitude and velocity of pupil contraction and lower values of duration of pupil contraction and latency, duration and velocity of pupil dilation.Conclusion: Static and dynamic pupil characteristics of subjects treated with silodosin for BPH is different from healthy eyes. In addition, our results may have shed light on understanding the risk for IFIS before cataract surgery and thus surgeons can be on the alert and take precautions.