Unveiling the antinociceptive mechanisms of Methyl-2-(4-chloro-phenyl)-5-benzoxazoleacetate: insights from nociceptive assays in mice.

OBJECTIVE: Methyl-2-(4-chloro- phenyl)-5-benzoxazoleacetate (MCBA), a synthetic benzoxazole derivative with established antipsoriatic efficacy, was investigated for potential antinociceptive effects. This study employs various nociceptive assays in mice to elucidate MCBA's antinociceptive mechanisms. MATERIALS AND METHODS: MCBA's antinociceptive potential was tested against various nociception models induced by formalin, glutamate, capsaicin, a transient receptor potential vanilloid 1 (TRPV1) receptor agonist, and phorbol 12-myristate 13-acetate, a protein kinase C (PKC) activator. It was then assessed using the hot plate test and examined within the acetic acid-induced writhing test. During the acetic acid-induced writhing test, MCBA was pre-challenged against selective receptor antagonists such as naloxone, caffeine, atropine, yohimbine, ondansetron, and haloperidol. It was also pre-challenged with ATP-sensitive potassium channel inhibitor (glibenclamide) to further elucidate its antinociceptive mechanism. RESULTS: The results showed that oral administration of MCBA led to a dose-dependent and significant inhibition (p < 0.05) of nociceptive effects across all evaluated models at doses of 60, 120, and 240 mg/kg. Moreover, the efficacy of MCBA's antinociceptive potential was significantly counteracted (p < 0.0001) by specific antagonists: (i) directed at adenosinergic, alpha-2 adrenergic, and cholinergic receptors using caffeine, yohimbine, and atropine, respectively; and (ii) targeting ATP-sensitive potassium channels, employing glibenclamide. Antagonists aimed at opioidergic and serotoninergic receptors (naloxone and ondansetron, respectively) had poor utility in inhibiting antinociceptive activity. Conversely, the dopaminergic receptor antagonist haloperidol potentiated locomotor abnormalities associated with MCBA treatment. CONCLUSIONS: MCBA-induced antinociception involves modulation of glutamatergic-, TRVP1 receptors- and PKC-signaling pathways. It impacts adenosinergic, alpha-2 adrenergic, and cholinergic receptors and opens ATP-sensitive potassium channels.

A prospective study of incidence and outcome of acute kidney injury among hospitalised patients in Malaysia (My-AKI).

INTRODUCTION: The incidence of acute kidney injury (AKI) among hospitalised patients has not been well studied in Malaysia. MATERIALS AND METHODS: We conducted a prospective, multicentre study in seven hospitals in West Malaysia. All the adults admitted in March 2017 fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI were included. RESULTS: Of the 34,204 patients screened, 2,457 developed AKI (7.18%), 13.1% of which occurred in intensive care unit (ICU). There were 60.2% males with a mean age of 57.8 (±17.5) years. The most common comorbidities were hypertension (55.0%), diabetes (46.6%), ischaemic heart disease (15.1%) and chronic kidney disease (12.0%). The commonest causes of AKI were sepsis (41.7%), pre-renal (24.2%) and cardiorenal syndrome (10.8%). Nephrotoxin exposure was reported in 31%. At diagnosis, the proportion of AKI stages 1, 2 and 3 were 79.1%, 9.7%, 11.2%, respectively. Referral to nephrologists was reported in 16.5%. Dialysis was required in 176 (7.2%) patients and 55.6% were performed in the ICU. Acidosis (46.2%), uraemia (31.6%) and electrolyte disturbance (11.1%) were the commonest indications. Continuous renal replacement therapy (CRRT) was required in 14%. The average length of hospital stay was 9.5 days. In-hospital mortality was 16.4%. Among survivors, full and partial renal recovery was seen in 74.7% and 16.4% respectively while 8.9% failed to recover. After a mean follow-up of 13.7 months, 593 (30.2%) of survivors died and 38 (1.9%) initiated chronic dialysis. Mortality was highest among those with malignancies (Hazard Ratio, HR 2.14), chronic liver disease (HR 2.13), neurological disease (HR 1.56) and cardiovascular disease (HR 1.17). CONCLUSION: AKI is common in hospitalised patients and is with associated high mortality during and after hospitalisation.

Pattern of biopsy-proven renal disease in Sabah: A retrospective cross-sectional study over 3.5 years.

OBJECTIVES: To explore the epidemiological and histopathological patterns of glomerular diseases in Sabah. METHODS: A state-wide cross-sectional study was conducted. There were 336 native renal biopsies in 296 eligible patients from 1st January 2013 to 30th June 2016. All patients aged ≥12 years with sufficient sampling (≥8 glomeruli) for histopathological assessment were included. Graft kidney biopsies, protocol-based biopsies and patients with uncertain demographics were excluded. Demographics of patients, clinical data, laboratory parameters prior to biopsy, and histology findings of renal biopsies were collected from local unit database and recorded into a standardised data collection form. Descriptive statistical analyses were employed and factors associated with Lupus nephritis (LN) were explored using logistic regression. RESULTS: The mean age during biopsy was 34.53 years (Standard Deviation 0.759). Primary glomerulonephritis (PGN) accounted for 42.6% (126) of all native renal biopsies. The commonest cause of PGN was minimal change disease (38.9%, 49) followed by focal segmental glomerulosclerosis (33.3%, 42) and IgA nephropathy (14.3%, 18). LN is the leading cause for secondary glomerulonephritis (SGN) (87.2%, 136). Younger age (Odds Ratio, OR 0.978; 95% Confidence Interval, 95%CI 0.960, 0.996); female gender (OR 17.53; p<0.001); significant proteinuria (OR 132.0; p<0.001); creatinine level at biopsy (OR 11.26; p=0.004); positive antinuclear antibody (ANA) (OR 46.7; p<0.001); and ANA patterns (OR 8.038; p=0.018) were significant in predicting the odds of having LN. CONCLUSION: This is the first epidemiology study of glomerular diseases in Sabah. The predominance of LN suggests lower threshold for renal biopsy in patients with suspected glomerular disorders. We have identified significant predictors for early detection and treatment of LN.

Newly diagnosed end stage kidney disease in a single centre in Sabah.

AIM: To study the epidemiology, clinical characteristics, vascular access, and the short term survival of ESRD patients initiated on dialysis from Hospital Queen Elizabeth (HQE). BACKGROUND: The number of patients with ESRD is increasing in Sabah, Malaysia. Most patients present late and some live in remote areas with difficult access to healthcare services. Many therefore present with potentially fatal complications. METHODS: All the newly confirmed ESRD patients who were initiated on renal replacement therapy (RRT) from 1 January to 31 December 2014 were included. The basic epidemiological and clinical data were collected. They were divided into three groups: Group 1 - those known to the medical service and had been prepared properly for the initiation of RRT; Group 2 - those known to the medical service, but were not prepared for the RRT; Group 3 - those with undiagnosed CKD. Outcome is mainly survival at 3rd, 6th, 9th and 12th month. RESULTS: There were 249 ESRD patients. 153 (61.4%) were male. The average age was 53.3 (range 12 - 83). The main cause of ESRD was diabetic nephropathy (128 patients, 51.4%). Most patients were started on RRT with a catheter (74.3%), 47 patients (18.9%) with a fistula, and 17 patients (6.8%) with a Tenckhoff catheter. 185 (74.3%) patients were not prepared properly (Group 2 - 66.3%, and Group 3 - 8.0%). The survival for 249 patients were 86.3% at 6 months, 77.9% at 12 months. Group 2 has the worst survival (81.9% at 6 months, 71.1% at 12 months). CONCLUSIONS: Our data showed that most patients (74.3%) were started on dialysis in an unplanned manner with poor survival. A comprehensive and well-supported predialysis programme is needed.

Issues in implementing a knowledge-based ECG analyzer for personal mobile health monitoring.

Advances in sensor technology, personal mobile devices, and wireless broadband communications are enabling the development of an integrated personal mobile health monitoring system that can provide patients with a useful tool to assess their own health and manage their personal health information anytime and anywhere. Personal mobile devices, such as PDAs and mobile phones, are becoming more powerful integrated information management tools and play a major role in many people's lives. We focus on designing a health-monitoring system for people who suffer from cardiac arrhythmias. We have developed computer simulation models to evaluate the performance of appropriate electrocardiogram (ECG) analysis techniques that can be implemented on personal mobile devices. This paper describes an ECG analyzer to perform ECG beat and episode detection and classification. We have obtained promising preliminary results from our study. Also, we discuss several key considerations when implementing a mobile health monitoring solution. The mobile ECG analyzer would become a front-end patient health data acquisition module, which is connected to the Personal Health Information Management System (PHIMS) for data repository.

A hybrid mobile-based patient location tracking system for personal healthcare applications.

In the next generation of Infocommunications, mobile Internet-enabled devices and third generation mobile communication networks have become reality, location based services (LBS) are expected to be a major area of growth. Providing information, content and services through positioning technologies forms the platform for new services for users and developers, as well as creating new revenue channels for service providers. These crucial advances in location based services have opened up new opportunities in real time patient tracking for personal healthcare applications. In this paper, a hybrid mobile-based location technique using the global positioning system (GPS) and cellular mobile network infrastructure is employed to provide the location tracking capability. This function will be integrated into the patient location tracking system (PLTS) to assist caregivers or family members in locating patients such as elderly or dependents when required, especially in emergencies. The capability of this PLTS is demonstrated through a series of location detection tests conducted over different operating conditions. Although the model is at its initial stage of development, it has shown relatively good accuracy for position tracking and potential of using integrated wireless technology to enhance the existing personal healthcare communication system through location based services.

Distributed personal health information management system for dermatology at the homes for senior citizens.

A distributed personal health information management system (D-PHIMS) has been tested at a nursing home for the senior citizens (NHSC) in Singapore. The personal health information management system (PHIMS) from the University of Washington was customized to Singapore's context for teledermatology. A clinical trial commenced in October 2005 is ongoing and the survey results obtained indicate that the participants are satisfied with the D-PHIMS system. The diagnosis and treatment recommendations made by the dermatologists using the D-PHIMS diagnosis module were effective in most cases based on feedback from the nursing staff at the elderly nursing home. The results suggest that a teledermatology system could become a useful tool for the nursing homes and to control increasing healthcare costs for elderly care.