K2P channels and their protein partners.

A decade since their discovery, the K2P channels are recognized as pathways dedicated to regulated background leakage of potassium ions that serve to control neuronal excitability. The recent identification of protein partners that directly interact with K2P channels (SUMO, 14-3-3 and Vpu1) has exposed new regulatory pathways. Reversible linkage to SUMO silences K2P1 plasma membrane channels; phosphorylation of K2P3 enables 14-3-3 binding to affect forward trafficking, whereas it decreases open probability of K2P2; and, Vpu1, an HIV encoded partner, mediates assembly-dependent degradation of K2P3. An operational strategy has emerged: tonic inhibition of K2P channels allows baseline neuronal activity until enhanced potassium leak is required to suppress excitability

Charybdotoxin binding in the I(Ks) pore demonstrates two MinK subunits in each channel complex.

I(Ks) voltage-gated K(+) channels contain four pore-forming KCNQ1 subunits and MinK accessory subunits in a number that has been controversial. Here, I(Ks) channels assembled naturally by monomer subunits are compared to those with linked subunits that force defined stoichiometries. Two strategies that exploit charybdotoxin (CTX)-sensitive subunit variants are applied. First, CTX on rate, off rate, and equilibrium affinity are found to be the same for channels of monomers and those with a fixed 2:4 MinK:KCNQ1 valence. Second, 3H-CTX and an antibody are used to directly quantify channels and MinK subunits, respectively, showing 1.97 +/- 0.07 MinK per I(Ks) channel. Additional MinK subunits do not enter channels of monomeric subunits or those with fixed 2:4 valence. We conclude that two MinK subunits are necessary, sufficient, and the norm in I(Ks) channels. This stoichiometry is expected for other K(+) channels that contain MinK or MinK-related peptides (MiRPs)

Sumoylation silences the plasma membrane leak K+ channel K2P1.

Reversible, covalent modification with small ubiquitin-related modifier proteins (SUMOs) is known to mediate nuclear import/export and activity of transcription factors. Here, the SUMO pathway is shown to operate at the plasma membrane to control ion channel function. SUMO-conjugating enzyme is seen to be resident in plasma membrane, to assemble with K2P1, and to modify K2P1 lysine 274. K2P1 had not previously shown function despite mRNA expression in heart, brain, and kidney and sequence features like other two-P loop K+ leak (K2P) pores that control activity of excitable cells. Removal of the peptide adduct by SUMO protease reveals K2P1 to be a K+-selective, pH-sensitive, openly rectifying channel regulated by reversible peptide linkage

A CASE SERIES OF EUCALYPTUS OIL-INDUCED SEIZURES

Eucalyptus oil (EO) is an essential oil which has been used as a traditional remedy in upper respiratory tract infection. It contains approximately 90% cineole and is readily available worldwide in over-the-counter cough drops, liniments, toothpaste, mouthwashes, cold preparations, and hair lice remover. EO-induced adverse drug reaction is rare in both adults and children. The signs and symptoms of EO poisoning are CNS depression, hypotension, tachycardia, epigastric pain, nausea, vomiting, and contact dermatitis. Symptom onset is usually rapid and resolves within 24 h. We report the case series of four adult patients with EO-induced seizure in India, who inhaled EO for common cold and presented to the critical care with single first attack of generalized tonic-clonic seizures. On further evaluation, none of them had a family background of seizures/febrile seizures. EEG and brain MRI were found to be normal in all patients. All the patients were managed with anti-epileptic drugs and standard supportive care. All medical practitioners should be aware of the toxic effects of EO, a common OTC medication used in Indian households. Warning labels may be attached on EO comprised products

Effect of Baladi Thalam in the management of Ardhavabhedaka (Migraine)

Almost all our ancient Acharayas have mentioned about the Shiro-roga of which Shirah-shoola as the main symptom and also they have taken Shirah-shoola as the synonym of Shiro-roga. all the Acharyas have mentioned Ardhavabhedaka in Shiro-roga. Acharya Sushruta has mentioned 11 types of Shiro-roga in Uttar Tantra. Among them, one of them is Ardhavabhedaka in which paroxysmal unilateral headache associated with vertigo and pain of varying intensity is seen. This can be correlated with Migraine. In the present era, a boom in the Alternative and Complementary systems of medicine has led to deep introspection of their utility based on scientific validation. Hence it is the need of the hour to establish a firm clinical research based scientific data for classical treatments. Thalam is one such treatment modality implicated for the use in Shiroroga. An attempt has been made in the present clinical research to assess the effect of Baladi Thalam in the management of Migraine (Ardhavbhedaka). Total 30 patients were registered. Result of the study revealed that Baladi Thalam therapy is effective in reducing the sign and symptoms as well as physical assessment

Early postoperative outcomes of dunking pancreatojejunostomy

Background: There is no gold standard method for pancreatico-enteric reconstruction.  In our department, dunking pancreatojejunostomy (DPJ) and Duct to mucosa PJ technique are done as per surgeon’s choice.  In this study, authors evaluate the early postoperative outcomes following DPJ based on ISGPS (2007).Methods: A Retrospective analysis of prospectively collected data from January 2008 to December 2015. Detailed information on these patients was maintained on a prospectively held computerized database. Routine drain amylase estimations are being done on POD 3and 5 for all patients undergoing pancreatic resections and on all subsequent days if output is suggestive of pancreatic fistula. Details of patients who have undergone pancreatic resection with duct to mucosa type of pancreato-intestinal anastomosis during the same period (64 patients) were also collected prospectively and analysed. DPJ and Duct to mucosa groups were not comparable with respect to age, duct size, pancreatic gland texture and co-morbidities. Hence direct comparison between the two groups has not been carried out.Results: A total of 75 of 139 pancreatic resections with pancreatointestinal anastomosis who had dunking PJ and fulfilled the study criteria were analysed; none were excluded for analysing early outcomes. 19 out of 75 (25.5%) developed grade ‘A’ POPF, five out of 75 (6.6%) developed Grade ‘B’ POPF and three out of 75 (3.3%) developed Grade ‘C’ POPF. 20 out of 75 (26.6%) had grade ‘A’ DGE, five out of 75 (6.6%) had grade ‘B’ DGE. PPH occurred in four out of 75 (5.3%), two out of four were early PPH, one was managed by coiling and other by re-laparotomy, two were late PPH both managed by coiling of the pseudo aneurysms. There was no 30-day mortality.Conclusions: Dunking (Invagiantion) pancreatojejunostomy has accepatable early outcomes with clinically significant/relevant postoperative pancreatic fistula rates of Grade B (6.6%) and Grade C (4%), delayed gastric emptying (33.2%) and post pancreatic hemorrhage (5.3%) rates. The outcomes are comparable with Duct-to-mucosa PJ mentioned in literature

Evaluation of response to combination therapy with enalapril and torasemide in dogs with mitral valve disease

The present study was carried out with the objective of evaluating the response to a combination therapy of enalapril and torasemide in dogs with mitral valve disease (MVD). Dogs diagnosed with stage C of MVD as per the American College of Veterinary Internal Medicine guidelines were included in the study. Treatment was initiated with enalapril at 0.5 mg/kg BID and torasemide at 0.2 mg/kg OD orally on 0th day. Detailed clinical examination with special reference to the cardiovascular system including measurement of blood pressure, radiographic, electrocardiographic and echocardiographic parameters of the animals were performed on 0th and 30th day of treatment. The treatment was well tolerated by all the animals. Amelioration of clinical signs with a noticeable reduction in cough was noticed in all the animals. On 30th day of treatment, a significant decrease was noticed in the vertebral heart score and left ventricular internal diameter during diastole and a non-significant decrease was noticed in left atrium to aortic root ratio, left ventricular internal diameter during systole, with a considerable reduction in severity of mitral regurgitation. Post- treatment clearing of lung fields was noticed in dogs with radiographic evidence of pulmonary oedema on 0th day. In addition to this, ventricular premature complexes noticed in three animals pre- treatment was not noticed post treatment

Haemato-biochemical and trichographic studies on mucocutaneous lesions in dogs

The present study was carried out with the objective of assessment of haematobiochemical and trichographic features of mucocutaneous lesions in dogs. Dogs presented with mucocutaneous lesions associated with various dermatological conditions were included in the study. Mange, atopic dermatitis, dermatophytosis, juvenile cellulitis, pyoderma and hypothyroidism with secondary Malassezia dermatitis were presented with mucocutaneous lesions in the perioral, periorbital and in the nostrils with least involvement of anogenital region. Haemato-biochemical analysis revealed anaemia, non-significant increase in total leucocyte count, neutrophilia, eosinophilia, elevated platelet count, hyperproteinaemia and hypoalbuminaemia. Elevated serum C-reactive protein was evident in all cases. Trichographic features revealed that highest number of hairs were included in the telogen phase of hair cycle with greater number of primary hairs. Hair fractures were evident in 20.8 per cent of hairs and trichoptilosis of hair tip was observed in 50.8 per cent of hairs studied. Demodex mites could be detected by hair pluck examination in all cases of demodicosis

Evaluation of oxidative stress and efficacy of antioxidant therapy in dogs with haemorrhagic gastroenteritis

The present study was conducted to evaluate the alterations in oxidative stress parameters in dogs suffering from haemorrhagic gastroenteritis (HGE). Dogs presented with vomiting and diarrhoea were screened and fifteen animals with signs suggestive of HGE were included in the study. The oxidative stress parameters, serummalondialdehyde (MDA) level, total antioxidant status (TAS) and plasma glutathione peroxidase (GSH-Px) activity were studied. The values were compared with the values from six apparently healthy dogs. A significant increase was noticed in the mean values of serum MDA and TAS of diseased animals at the time of presentation when compared to healthy animals whereas the activity of plasma GSH-Px was found to be lower than in healthy dogs. Supplementation with N-acetyl cysteine @ 70 mg/kg or five days was found effective in managing the oxidative injury in the affected animals