Rheumatoid arthritis therapies: present and future

Rheumatoid arthritis [RA] is an autoimmune disorder characterized by inflammation of synovium, cartilage damage and co-occurring of various other disorders. Significant improvement has been achieved in RA therapeutics in last two decades. However, newer, more efficient and more cost-effective therapeutic applications are still needed to be developed. Current therapies in RA are mostly acting to restrict inflammation. Non steroidal anti inflammatory drugs [NSAIDs] and disease modifying antirheumatic drugs [DMARDs] are conventionally used in RA therapy. Studies showed higher efficacy of anticyfokine therapy such as anti-IL-6 and anti-TNF. Rituximab, targeting B cells, after establishing its potential was approved to be used in combination with methotrexate in 2006. Abatacept, CLTA-4-IgGl, has been developed to block CD28 and CD80 or CD86 interaction leading to the termination T cell activation. Molecular inhibitors are relatively new in RA therapeutics such as tocilizumab, tofacitinib and baricitinib. PDA has approved tofacitinib to be used as a treatment for moderate and severe RA. Future holds promising therapeutic options based on numerous studies. IL-12, IL-17 and IL-23 are the targets of future anticytokine therapies. Several lymphocyte targeting agents including ofatumumab, ocrelizumab and veltuzumab have been developed and are currently in phase II and phase III clinical trials. There is a vast range of potential targets in RA enabling us to expand the therapeutic options over the next decade

Glycated hemoglobin [HbA1c]; screening for undiagnosed diabetes in healthy individuals in Sargodha

HbA1c gives an integrated index of glycemia over the entire 120 days life span of red blood cells. Therefore, measuring HbA1c would be appropriate in diagnosing a disease characterized by chronic hyperglycemia and a gradual progression to complications. our primary objective was to evaluate the use of HbA1c as screening test for undiagnosed diabetes [WHO criteria of Fasting plasma glucose [FPG] of >/= 7mmol/l [126mg/dl]] in healthy asymptomatic individuals in Pakistani population. A cross sectional population survey was carried on asymptomatic, healthy individuals without past history of diabetes. Venous blood was obtained to measure fasting plasma glucose [fasting > 8 hours] and Hb A1c. Khan lab Sargodha from July 2013 to March 2014. It was performed by using NycoCard HbA1c in vitro diagnostic medical device for quantitative determination of glycated hemoglobin in whole blood. In our sample size of 775, the lowest HbA1c was found to be 5% and Highest 13.2%. Arithmetic means was 6.7565%, while the median value was 6.2% and standard deviation 1.3323. When using FPG only, the detection rate of diabetes was 32.65% [female, 14.71%; male, 17.94%]. When HbA1c was included as a diagnostic test, the detection rate increased to 40% [female, 18.84%; male, 21.16 %]. An additional 7.6% of participants were diagnosed with diabetes when using HbA1c criteria. ROC [A receiver operating characteristic] curve was used for analysis. At HbA1c cutoff of >/=6.5% it demonstrated sensitivity of 98.02% [95% CI] and specificity of 88.12% [95% CI] for detection of undiagnosed diabetes mellitus in healthy asymptomatic individuals in Pakistani population. Area under the ROC curve was 0.981354 with significance level P [Area=0.5] 0.0001. Our study reveals that HbA1c is a highly specific and convenient alternative to fasting plasma glucose for screening of diabetes mellitus in Pakistani population. A large scale survey should be carried out to set our own national standardizations

Signaling pathway involved in Rheumatoid Arthritis: target for new therapeutic interventions

Rheumatoid arthritis is categorized as a systematic autoimmune disease which causes chronic disabilities exclusively in bones that are aligned with synovium. RA etiology is still unknown but previous studies have coined that several number of factors play a significant role e.g. environmental and genetic factors. Cellular signaling pathways orchestrate the inflammatory response that regulates various cellular functions like cellular progression, proliferation, death and secretion of signaling molecules [pro and anti inflammatory cytokines] in response to genetic and environmental stimuli. These regulatory pathways are tightly controlled and naturally activated by ligands that attach to their respective receptors on the cell surface. In diseased state, these signaling pathways escape the normal control mechanisms resulting in intensification of cytokines and chemokines, transcription factors and mediatory proteins that disrupt normal cell processes and might bring about auto-destructive consequences such as in the case of rheumatoid arthritis. The review highlights multiple levels of targeting molecules in signaling pathways that may be potential diagnostic markers and also attempts to underline potential therapeutic targets

Vitamin D status; the epidemiology in Sargodha

Our primary objective was to estimate the vitamin D status among both the rural and urban dwellers of Sargodha. A cross sectional population survey. Individuals were selected from six different medical centers in the Sargodha city, Vitamin D measurement was done in Khan Lab Sargodha from January 2013 to June 2013. After an awareness campaign, healthy individuals and medical patients from six different clinics in Sargodha city were selected after excluding the diseases that interfered with the metabolism of calcium and vitamin D. The initial assessment involved an interview based questionnaire, at the clinic by the treating doctor. It recorded the information regarding age, sex, weight, residence, and co-morbid conditions like, DM, hypertension, ischemic heart disease and kidney disease and medications especially oral vitamin D supplementation. The physical assessments included height, weight record and blood pressure measurements. It was performed in Khan Lab Sargodha. Quantitative determination of 25-OH vitamin D was done from the serum by using competitive immunoluminometric assay on Maglumi 1000 fully automated chemistry analyzer. Out of total 100 specimens 46 were found to be having low levels of vitamin D levels. Insufficient levels [21-29 ng/ml] were present in 10 individuals. It was less than 10 ng/ml in 11, less than 5 ng/ml in 4, while 21 individuals were having levels between 10-20 ng/ml. Five individuals had levels more than 100 ng/ml. None of the individuals had level in toxic range. Out of 56 females 27[48.22%] had low vitamin D levels, while out of 44 males 19 [43.2%] were found to be having levels less than 30ng/ml. The median age of individuals having levels less than 30ng/ml was 37 years [14-57 years]. The relationship of high BMI and vitamin deficiency was statistically non-significant [p-value = .282]. Although the sample size is small, however our study reveals that a large proportion [46%] of studied individuals representing the asymptomatic general population is having low level of vitamin D. in order to address this public issue concrete measures need to be taken in order to prevent adverse consequences of low vitamin D levels

Pulmonary tuberculosis; frequency of smear positive in private laboratories of Sargodha outside the TB-DOTS programme

To assess the frequency of smear positive pulmonary tuberculosis patients diagnosed at private laboratories of Sargodha not included in the national DOTS [Direct Observational Therapy Short Course] programme. A retrospective study. Private laboratories of Sargodha from January 2007 to December 2012. Data analysis of 3952 patients who reported to private laboratories of Sargodha for staining of sputum for AFB was carried out. They were all self reporting and were either suspects of pulmonary tuberculosis or had a history of contact with a smear positive case of TB. Staining was done by Ziehl-Neelson method. The smear results were reported as positive or negative. Out of total 3952 specimens 373 [9.21%] were found to be positive for the presence of acid fast bacilli. From these 373 positive cases 164 [44%] were female and 209 [56%] were males. The age group most frequently associated with the smear positive result was aged > 55 years [13.89%] followed by age < 15 years [10%]. A large number of smear positive patients are diagnosed in private sector. These patients are not registered in DOTS programme of World Health Organization. Their number is not included in the calculating the prevalence TB in our country. It is recommended that TB case notification should be made mandatory by law by private sector health care providers

Immunoreactivity of proliferating cell nuclear antigen in transitional cell carcinoma of urinary bladder

This is a descriptive study designed to evaluate Proliferating cell nuclear antigen [PCNA] in transitional cell carcinoma. A total of fifty per urethra resected bladder tumour samples [TUR BT] were collected from Mayo Hospital and Services Hospital, Lahore and processed for H and E and PCNA stain. The grading of tumours were made on H and E stain. While Proliferating cell nuclear antigen labeling index was recorded for each case. The mean PCNA labeling index was significantly higher in grade III when compared with tumours of grade II. [p < 0.001] carcinoma. Similarly mean PCNA labeling index was significantly higher [p < 0.05] in patients having duration of symptoms up to 3 month when compared with the patients having longer duration of symptoms. The mean PCNA labeling index had significantly higher value in high grade tumours as compared to low grade tumours [p < 0.001]. Although determination of PCNA labeling index is costly yet it has significant role in tumour grading