Control of sodium and potassium homeostasis by renal distal convoluted tubules

Distal convoluted tubules (DCT), which contain the Na-Cl cotransporter (NCC) inhibited by thiazide diuretics, undergo complex modulation to preserve Na+ and K+ homeostasis. The lysine kinases 1 and 4 (WNK1 and WNK4), identified as hyperactive in the hereditary disease pseudohypoaldosteronism type 2, are responsible for activation of NCC and consequent hypokalemia and hypertension. WNK4, highly expressed in DCT, activates the SPAK/OSR1 kinases, which phosphorylate NCC and other regulatory proteins and transporters in the distal nephron. WNK4 works as a chloride sensor through a Cl- binding site, which acts as an on/off switch at this kinase in response to changes of basolateral membrane electrical potential, the driving force of cellular Cl- efflux. High intracellular Cl- in hyperkalemia decreases NCC phosphorylation and low intracellular Cl- in hypokalemia increases NCC phosphorylation and activity, which makes plasma K+ concentration a central modulator of NCC and of K+ secretion. The WNK4 phosphorylation by cSrc or SGK1, activated by angiotensin II or aldosterone, respectively, is another relevant mechanism of NCC, ENaC, and ROMK modulation in states such as volume reduction, hyperkalemia, and hypokalemia. Loss of NCC function induces upregulation of electroneutral NaCl reabsorption by type B intercalated cells through the combined activity of pendrin and NDCBE, as demonstrated in double knockout mice (KO) animal models, Ncc/pendrin or Ncc/NDCBE. The analysis of ks-Nedd-4-2 KO animal models introduced the modulation of NEDD4-2 by intracellular Mg2+ activity as an important regulator of NCC, explaining the thiazide-induced persistent hypokalemia.

Medical devices associated adverse events under Materiovigilance Programme of India in a Tertiary Care Hospital of Tribal District of Odisha

Background: A materiovigilance program is a system that is used for the identification, collection, and reporting of possible adverse reactions resulting from the use of medical devices. This monitoring program ensures the safety of patients and aids the post-marketing surveillance process. The Materiovigilance Programme of India (MvPI) was launched on July 6, 2015. Aims and Objectives: The primary objective of the study was to generate evidence based data on the safety of the medical devices used in our institute and to analyze the risk benefit ratio of reported adverse events of medical devices and to communicate the safety information to the stake holders. The secondary objective was to educate and advocate the concept of MvPI and creating a culture of adverse events reporting among health workers. Materials and Methods: A retrospective study was conducted after receiving clearance from the Institutional Ethical Committee, Saheed Laxman Nayak Medical College and Hospital (SLN MCH), Koraput. Data about Medical Device-Associated Adverse Events (MDAEs) were collected from MDMC, SLN MCH, Koraput, for the period from October 2019 to February 2022. MDAE reports were collected by a materiovigilance associate during the period from October 2019 to February 2022. Events were reviewed to verify whether or not they were documented in patient’s electronic records and a database of devices was created, which included the events associated with each device. Device-related MDAEs were classified by patient characteristics and the medical devices used. Results: In the 15-month study period, a total of 56 cases of MDAE were reported to MDMC, SLN MCH, Koraput. Of these, 17.9% MDAEs (10 cases) were adverse events related to surgical gloves, 8.9% (five cases) were associated with pulse oximeters, 7.14% of cases (4 cases) were due to glucometer malfunctioning, and 7.1% were related to HIV diagnostic kits such as false positives and false negatives. Adverse events such as skin rashes, irritation on skin, itching, redness of eyes, and gum bleeding in patients with dental braces were reported. A majority of device defects involved inaccuracy in the data reported by the devices (seen in 10.7% of cases), while six cases were due to device malfunctioning. Conclusion: This study shows only the tip of iceberg of the reporting trends of MDME. There is inequality in reporting by different grades of health care workers and from different departments. It highlights the necessity of conducting awareness programs, training and workshops regularly. Device-related safety and reporting of device-related adverse events should be subject of attention and further research.

Computed Tomography Scan And Therapeutic Response In Patients With Neurocysticercosis.

Neurocysticercosis (NCC) is the most common parasitic disease of the nervous system with varied clinical and imaging spectrum. This study was conducted to describe the clinical , CTfinding and response to therapy of NCC. Materials: Hundred (100) patients of NCC presenting in department of medicine, PMCH, Patna were evaluated on preset proforma containing detailed demographic data, dietary habits, clinical features and neuroimaging findings and its therapeutic response. Patients were treated with 28 days course of albendazole and repeat CTscan was done in 2 months after treatment. Results: Out of 100 patients of NCC, 56 (56%) were male with most common age group being 21-30 years (36%). Only Seizure is the most common presentation followed by Seizure with featuers of increased intracranial pressure (70 and 14% respectively). Multiple ring enhancing lesions either alone or in combination were seen on computerised tomography scans in 56 (56%) cases and parietal lobe involvement is the commonest site. Complete resolution of CTscan lesions in 72 (72%) and partial resolution occurred in rest of patients. Conclusions: Neurocysticercosis is common public health problem and one of the common cause of seizure. It has varied imaging finding being ring enhancement is most common. Albendazole is highly effective therapy and should be started at earliest to prevent morbidity and mortality

Cardiac Magnetic Resonance Findings In Left Ventricle Non Compaction: A Monocentric Study

BACKGROUND:TheimpactofLVNCindilatedcardiomyopathyandleftventriclesystolicdysfunctionis controversial .METHODS: A retrospective study of 46 patients, over a period of 09 years between September 2009 and December 2018, performed in the cardiology department “B”, IBN SINA hospital, Rabat, Morocco. RESULTS: The mean age was 44 ± 16 years with extremes ranging from 10 years to 97 years. A slight predominance of male with 54% was observed. In TTE only 17,4% of patients had a suspected LVNC. The mean LVEDD was 68.6 ± 8.4 mm. The mean LVEDV was 223.1 ± 76.3 ml with a maximum of 443 ml and a minimum of 122 ml. The mean LVEF was 37.1 ± 12.7. Akinesia was observed in 28% of patients involving the infero-septal wall in 97% of cases. The non compaction was located in anterolateral wall was involved in 97.8 % of cases, and the inferoseptal wall was always spared. The median NC/C ratio was 2.8 [2.5-3], with extremes ranging from 2.3 to 5. LGE was present in 59 % of our patients; mostly located in the infero-septal. In multivariate analysis, NC/C ratio correlates significantly with the presence of LGE in the infero-lateral wall and the apex respectively (p: 0.04 and p: 0.002). NC / C ratio correlates with LVEF (OR: 0.03, CI [0.01-0.04], p: 0.02). CONCLUSION: This study shows the CMR profile of LVNC Moroccan patients. Our results affirm that the NC/C ratio in LVNC is a major determinant of LV fiosis and systolic dysfunction.

A clinical study of new onset seizures in children aged 3-12 years

Background: Seizures are common in pediatric age group and less than 1/3rd of seizures in children are caused by epilepsy. Aim of present study was to analyze the etiological factors and clinical profile of new onset seizures in children aged 3-12 years.Methods: This was a prospective study done at a tertiary care center of south India. Authors analyzed 98 children aged 3-12 years presenting with new onset seizures. Proper history and investigations including EEG, and CT brain were done to confirm the etiology.Results: Out of 98 children 51 were 3-5 yrs of age and 47 were 6-12 years. 66.3% had generalized seizure and 33.6% had partial seizure. Partial seizure were more common in 5-12 years of age. Intracranial infections were the leading cause (73/98) which included neurotuberculosis (26/73), NCC (20), bacterial meningitis (12), cerebral malaria (8) and viral encephalitis (7). Intracranial infections' were the' leading cause in both age groups. Space occupying lesions were more common in 6-12 years (46.8%) as compared to 3-5 years (19.6%). NCC and Tuberculoma were the leading CT findings in both age groups. There was significantly high incidence of focal EEG changes in partial seizure group compared to generalized seizure group.Conclusions: Intracranial infections were leading cause of new onset seizures especially GTCS. Good clinical evaluation and judicious use of investigations should be ensured. CT brain and EEG are more likely to be informative in partial seizures than in generalized seizures.

Effect of extracellular potassium on the activity of distal renal tubule in mice / 上海交通大学学报（医学版）

Objective: To investigate the effect of extracellular potassium (K+) concentration on the activities of sodium chloride co-transporter (NCC) and large conductance Ca2+-activated K+ channel (BK) in distal renal tubule of mice. Methods: Six specific pathogen free (SPF) C57BL/6 mice aged 8 to 10 weeks were sacrificed,and the kidney slices were made with previously reported method. Then,these slices were incubated randomly in normal K+,high K+,BaCl2 and RbCl solutions,respectively. The abundance and phosphorylation level of NCC in kidney slices at different K+ concentrations and different time courses were detected by Western blotting. The overall and membrane expressions of BK in kidney slices were also detected after incubation with different K+ solutions for 2 h. Results: Compared with normal K+ solution,NCC phosphorylation level was significantly decreased after incubation with high K+ solution for 5,15,30 min (all P<0.05),and NCC phosphorylation level was also decreased after intervention with K+ channel inhibitor Ba2+ or Rb+ (both P<0.05). After the treatment with high K+ solution for 2 h,neither the overall cell expression of BKα subunit and β4 subunit,nor membrane expression of BKα subunit was found significant changes compared with normal K+ incubation. Conclusion: High K+ can directly down-regulate NCC phosphorylation level,which may be preparation for kaliuresis of the downstream tubule of distal convoluted tubule.

Pharmacovigilance programme of India: revival of the renaissance

Adverse drug reactions (ADRs) are the fourth leading cause of morbidity in the world. In order to safeguard the health of the community, Pharmacovigilance Programme of India (PvPI) is implemented as the monitoring body by Indian Pharmacopoeia Commission (IPC). It is leading national authority. National Coordinating Centre (NCC) PvPI works as the World Health Organization (WHO) collaborating centre for pharmacovigilance. Adverse drug reactions are reported to NCC PvPI which are then directed towards WHO Uppsala Monitoring Centre (UMC) Sweden which is the global monitoring centre for worldwide data. Central Drugs Standard Control Organization (CDSCO) is the regulatory authority of India under the Ministry of Health and Family Welfare (MOHFW), Government of India. This article focusses on the various strands of pharmacovigilance at the healthcare professional and consumer level. It also discusses the pitfalls in the journey of pharmacovigilance thus helping in enhancing the quality of health safety. Even a minuscule contribution by a health care professional or a consumer can voluminously help in promotion of drug safety. Therefore, there is a need of inculcating the culture of adverse drug reaction reporting for the welfare of the vulnerable masses.

Noninvasive Diagnostic Criteria of the Revised 2014 the Korean Liver Cancer Study Group and the National Cancer Center Guideline for Subcentimetersized Hepatocellular Carcinoma: Is It Too Strict?

BACKGROUND/AIMS: Noninvasive diagnostic criteria for hepatocellular carcinoma (HCC) differ between guidelines, especially for subcentimeter-sized nodules. This study aimed to analyze clinical and radiological characteristics of subcentimeter-sized HCC, and assess the validity of noninvasive diagnostic criteria of the revised 2014 the Korean Liver Cancer Study Group and the National Cancer Center (KLCSG-NCC) guideline for subcentimeter-sized HCC. METHODS: A total of 33 consecutive patients (median age, 58.6 years; men, 60.6%; hepatitis B virus-infected, 87.9%) who were diagnosed with HCC between January 2009 and December 2013 and had a maximum tumor diameter less than 1 cm were retrospectively included. RESULTS: Among 33 subcentimeter-sized HCC cases, 6 cases were histologically proven and the remaining 27 patients were diagnosed by radiologically and/or serologically. Initial detection modality was dynamic contrast-enhanced computed tomography (CT) (66.7%, 22/33) or dynamic contrast-enhanced magnetic resonance imaging (MRI) (33.3% 11/33). No case was identified by surveillance ultrasonography. Typical radiological feature of HCC, which is arterial enhancement with delayed washout, was present in 51.7% (15/29 patients) in dynamic contrast-enhanced CT, and 90.9% (30/33 patients) in dynamic contrast-enhanced MRI. When these 33 cases were re-assessed by the revised 2014 KLCSG-NCC guideline, no one has fulfilled the noninvasive diagnostic criteria. CONCLUSIONS: None of the cases that were diagnosed as subcentimeter-sized HCC including histologically confirmed cases did not fulfill the noninvasive diagnostic criteria of the revised 2014 KLCSG-NCC guideline. Refinement of the current noninvasive diagnostic criteria for subcentimeter-sized HCC may be required.

Adhesion of enolase and Tuf from B.longum NCC2705 / 军事医学

Objective To demonstrate that enolase and Tuf are direct adhesions of Bifidobacterium longum( B.longum) NCC2705.Methods B.lougum NCC2705 was co-cultured with Caco-2.The change of adhesion was tested by microscopy after the purified proteins(GST-Eno and GST-Tuf) were added into the co-culture, and then statistical analysis was conduc-ted.Caco-2 cells were incubated with B.lougum NCC2705 and pathogenic bacteria (Shigella flexneri 2a or Salmonella). The level ofcytokine LDH and TNF-αfor supernatant was tested after the purified proteins ( GST-Eno and GST-Tuf) were added.Results The number of bacteria adherent to Caco-2 was reduced significantly ( P <0.05 ) after the purified proteins ( GST-Eno/GST-Tuf) were added .While Caco-2 was co-cultured with pathogens , the level of LDH and TNF-αwas significantly increased (P<0.05).When Caco-2 was incubated with B.lougum NCC2705 and pathogenic bacteria , the level of LDH and TNF-αwas significantly reduced (P<0.05), but the level of LDH and TNF-αincreased once more (P<0.05) after the purified protein (GST-Eno/GST-Tuf) was added.Conclusion B.longum NCC2705 can competitive-ly inhibit production of pathogenic bacteria in intestinal epithelial cell adhesion , while the enolization enzyme and Tuf proteins can competitively inhibit long bifidobacteria in intestinal epithelial cell adhesion effect .They are adhesion factors of bifidobacteria .

Emergency Neuroendoscopic Management of Third Ventricular Neurocysticercosis Cyst Presented with Bruns Syndrome : Report of Two Cases and Review of Literature

Neurocysticercosis is the commonest parasitic disease of the human central nervous system. The incidence of intra ventricular form of neurocysticercosis (NCC) is less common accounting 10-20% that of total central nerve system cysticercosis. Intra ventricular NCC is complicated due, to its high incidence of acute hydrocephalus caused by ball valve mechanism. The only reliable tool for diagnosis of NCC is by neuroimaging with CT or MRI. MRI preferred over CT because of its high specificity and sensitivity. In emergency situations like acute hydrocephalus one can proceed with emergency endoscopic surgery. Through the endoscopic view, intra ventricular NCC (IVNCC) has distinguished morphological features like the full moon sign. This feature not only helps in identification of IVNCC, but also guides in further endoscopic treatment strategy. Authors report two cases of 3rd ventricular NCC with acute hydrocephalus managed with emergency endoscopy. Authors have discussed the clinical features, intra operative endoscopic findings and role of endoscopy in emergency surgery for NCC with acute hydrocephalus.

Role of Magnectic Resonance Imaging of Brain in Paediatric Patients with Partial Seizures.

The study was carried out for one year to find out the role of magnetic resonance imaging brain in pediatric patients with partial seizures. Children from age 28 days to 18 years who presented with partial seizures were included and the information obtained from the history, clinical examination and investigations particularly MRI brain were noted down and analyzed.Maximum numbers of patients were in the age group of 5-10 years (48.84%).27.91% had simple seizures and the rest 72.09%had complex partial seizures with none having secondary generalization. The risk factor for seizures were present in 54.19% of cases. Most of the lesions involved parietal region (44.19%) followed by temporal lobe involvement in 13.95%. 55.81% had findings of neurocysticercosis (NCC), 29.91% showed tuberculoma, 8.30% had normal MRI findings and 6.98% had findings suggestive of cerebritis, sturge weber syndrome and porencephalic cyst. 89.74% lesions showed contrast enhancement on MRI. Contrast enhancement MR altered the radiological diagnosis in many patients with partial seizures. It helped to diagnose infections like tuberculoma and NCC in various stages of evolution and also helped to rule out other structural lesions, thus helping in planning modalities of treatment.

Chemotherapy outcome of patients with choriocarcinoma / Монголын Анагаах Ухаан

Background: Choriocarcinoma 15-20 new cases per year diagnosed at National Cancer Center of Mongolia. Due to insufficient necessary new drugs for choriocarcinoma patients, cancer center cannot provide the most useful treatment EMA/CO so patients were treated MAC or metothrexate, Adriamycin and cyclophosphamide. The outcomes of patients with choriocarcinoma treated with combined chemo drugs never been studied in Mongolia. Goal: To evaluate the results of combined chemotherapy in choriocarcinoma at National Cancer Center of Mongolia. Methods: Retrospective cohort review of 42 patients with choriocarcinoma who treated with MAC combination chemotherapy at NCC of Mongolia during 2004-2007. Based on MAC ppatients charts we evaluated clinical characteristics, level of HCG during treatment cycles, ultrasound changes and other lab tests. Results: We treated 42 patients with choriocarcinoma from 2004 through 2007. All patients were treated with MAC combination chemotherapy at NCC. The number of cases with choriocarcinoma is increasing in each year. 37.5% of these patients were aged between 30-34 years old, so it shows maximum incidence occurs during child bearing years. The most common clinical characteristics were 44% bleeding, 32% lower abdominal quadrant pain related to disease stages, 36% cough, and 28% fever. Out of 42 patients 35% of them had lung metastasis which was significantly different than other gynecological cancer metastasis. Conclusion: MAC combination treatment offers long-term disease-free survival and potential cure in patients with choriocarcinoma. The reported median survival in these group patients is 5 years. Importantly, 56% of patients were lived up to 5 years in remission.

Neurocysticercosis in children.

Neurocysticercosis (NCC) is a common cause of seizures and neurologic disease. Although there may be variable presentations depending on the stage and location of cysts in the nervous system, most children (> 80%) present with seizures particularly partial seizures. About a third of cases have headache and vomiting. Diagnosis is made by either CT or MRI. Single enhancing lesions are the commonest visualization of a scolex confirms the diagnosis. Some cases have multiple cysts with a characterstic starry-sky appearance. Management involves use of anticonvulsants for seizures and steroids for cerebral edema. The use of cysticidal therapy continues to be debated. Controlled studies have shown that cysticidal therapy helps in increased and faster resolution of CT lesions. Improvement in long - term seizure control has not yet been proven. Children with single lesions have a good outcome and seizure recurrence rate is low. Children with multiple lesions have recurrent seizures. Extraparenchymal NCC has a guarded prognosis but it is rare in children. In endemic areas NCC must be considered in the differential diagnosis of seizures and various other neurological disorders.

Comparison on accuracy of porcelain color reproducibility using two colorimeters / 대한치과보철학회지

STATEMENT OF PROBLEM: Although the use of colorimeter to improve the accuracy of tooth color measurement has increased, it is real situation that there is almost no comparative study about the accuracy among various colorimeters. PURPOSE: The purpose of this study is to compare the accuracy of porcelain color reproducibility using ShadeEye-Ncc dental chroma meter (Shofu Inc., Kyoto, Japan) and Shadepilot(TM) system (Degudent Inc., Hanau, Germany). MATERIAL AND METHODS: Color of 2M2 and 3M2 shade tap of Vitapan 3D Master shade guide were measured using the above two colorimeters. Porcelain specimens were fabricated through this data. The porcelain systems used were Vintage Halo Porcelain system with ShadeEye-Ncc dental chroma meter, and VitaOmega900 Porcelain system with Shadepilot(TM) system. Colors of shade tap models and porcelain specimen were measured with spectrophotometer, and calculated delta E based on the results. RESULTS: The following results were obtained. 1. Shadepilot(TM) system showed more suitable porcelain color reproducibility compared to ShadeEye-Ncc dental chroma meter (P < .05). 2. The result showed the difference of porcelain color reproducibility according to shade of Shade tap which is model. More suitable porcelain color reproducibility was shown at 3M2 shade tap than at 2M2 shade tap (P < .05). 3. The average of DeltaE* of porcelain specimens which was made by the two colorimeters was 4.44-6.14, so the difference of shade was shown through the naked eye. CONCLUSION: Shadepilottrade mark system showed more suitable porcelain color reproducibility. When using ShadeEye-Ncc dental chromameter, it will be necessary to improve accuracy through coloring various parts of the whole tooth.

Evaluation of shade guide using digital shade analysis system / 대한치과보철학회지

STATEMENT OF PROBLEM: There are two methods of color choice for the esthetic restoration. One is visual shade matching which draws a comparison between shade guide and teeth in dentist's own eye and the other is using a digital shade analysis system recently introduced. Although the visual shade matching has a lot of problems, decision of color by this visual shade matching and the ways of expression for the decided color are still applicable to clinical dentistry. PURPOSE: This study is designed to investigate shade guides used in the dental clinics and laboratories have the same value using ShadeEye-NCC(R). dental chroma meter (Shofu Inc., Kyoto, Japan) using shade guide are evaluated. MATERIAL AND METHODS: At the first experiment, eight Vita Lumin Vacuum shade guides (Vident Inc., California, USA) were collected from the dental clinics. A1 and B1 shade tabs are chosen and the colors are analyzed five times each in both tooth and porcelain modes by digital shade analysis system, ShadeEye-NCC(R). In the second experiment, twelve Vita shade guides using practically in the dental clinics and laboratories were collected and also A1 and B1 shade tabs are chosen and the colors of A1 and B1 are analyzed one time each in both tooth and porcelain modes by ShadeEye-NCC(R). RESULTS AND CONCLUSION: There were significant differences among eight shade guides in terms of shade (chroma), value and hue in both of A1 and B1 (P < .05). Shade guides using in present both dental clinics and laboratories did not show significant differences, except A1 in the porcelain mode, it showed significant differences (P < .05) in the shade even though the shade tab has the same name.

Regulation of Th1 and Th2 Type Cytokines in the NCC Patients Treated with Praziquantel / 热带医学杂志

Objective To explore immunological mark and the outcome of disease after pharmacological treatment in human NCC with praziquantel. Methods 35 patients were treated with praziquantel for 6 months. Levels of serum IL-2,IFN-γ, IL-12, IL-5, IL-10 and TNF-α were measured before and after treatment. Results Th1 type cytokines IL-2, IFN-γand IL-12 were up regulated after treatment( P ＜ 0. 01 ) . Levels of TNF-α and Th2 type cytokines IL-5 and IL-10 were remarkable decreased after treatment( P ＜ 0. 01 ). The levels of IL-2, IFN-γ and IL-12 from the patients with good response to the treatment is higher than those with no response to the treatment. Conclusion Th1 type cytokines were up regulated while Th2 type cytokines were down regulated in the NCC patients treated with praziquantel. The protective immunity may be related to the Thl cell activation.

Chronic Furosemide Administration Alters Abundance of Sodium Transporters in Rat Kidney / 대한신장학회잡지

BACKGROUND: Furosemide inhibit NaCl absorption in the thick ascending limb and produce an increase in distal delivery of Na+. We carried out semiquantitative immunoblotting and immunohistochemistry of rat kidneys to investigate whether chronic furosemide infusion is associated with compensatory increases in the abundance of Na+ transporters in distal nephron. METHODS: Osmotic minipumps were implanted into Sprague-Dawley rats to deliver 12 mg/day of furosemide(n=6) with simultaneous administration of 0.8% NaCl and 0.1% KCl in drinking water for 7 days. RESULTS: Compared with vehicle infused controls, urine volume and urine sodium amount were increased. However, there were no differences in body weight, serum aldosterone, and creatinine clearance. The abundance of Na+-K+-2Cl- cotransporter after furosemide infusion was increased in cortex (151+/-10 vs. 100+/-10%, p< 0.05) and outer medulla (122+/-5 vs. 100+/-3%, p< 0.01). In furosemide infusion group, the abundance of all three subunits of epithelial sodium channel (ENaC) was increased both in cortex (alpha: 187+/-25 vs. 100+/-17%, p< 0.05; beta: 155+/-8 vs. 100+/-15%, p< 0.05; gamma: 168+/-16 vs. 100+/-9%, p< 0.05) and outer medulla (alpha: 171+/-27 vs. 100+/-17%, p< 0.05; beta: 986+/-91 vs. 100+/-33%, p< 0.01; gamma: 242+/-24 vs. 100+/-22%, p< 0.01). Consistent with these results, ENaC beta-subuint immunohistochemistry showed a remarkable increase in immunoreactivity in the principal cells of collecting ducts with furosemide treatment. CONCLUSION: These increases in the abundance of ENaC protein may account for the generation of diuretic tolerance.