From cytokines to chemokines: Understanding inflammatory signaling in bacterial meningitis.

Bacterial meningitis is a serious central nervous system (CNS) infection, claiming millions of human lives annually around the globe. The deadly infection involves severe inflammation of the protective sheath of the brain, i.e., meninges, and sometimes also consists of the brain tissue, called meningoencephalitis. Several inflammatory pathways involved in the pathogenesis of meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis, Escherichia coli, Haemophilus influenzae, Mycobacterium tuberculosis, Streptococcus suis, etc. are mentioned in the scientific literature. Many in-vitro and in-vivo analyses have shown that after the disruption of the blood-brain barrier (BBB), these pathogens trigger several inflammatory pathways including Toll-Like Receptor (TLR) signaling in response to Pathogen-Associated Molecular Patterns (PAMPs), Nucleotide oligomerization domain (NOD)-like receptor-mediated signaling, pneumolysin related signaling, NF-κB signaling and many other pathways that lead to pro-inflammatory cascade and subsequent cytokine release including interleukine (IL)-1ß, tumor necrosis factor(TNF)-α, IL-6, IL-8, chemokine (C-X-C motif) ligand 1 (CXCL1) along with other mediators, leading to neuroinflammation. The activation of another protein complex, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome, also takes place resulting in the maturation and release of IL-1ß and IL-18, hence potentiating neuroinflammation. This review aims to outline the inflammatory signaling pathways associated with the pathogenesis of bacterial meningitis leading to extensive pathological changes in neurons, astrocytes, oligodendrocytes, and other central nervous system cells.

Quest for malaria management using natural remedies.

Malaria, transmitted through the bite of a Plasmodium-infected Anopheles mosquito, remains a significant global health concern. This review examines the complex life cycle of Plasmodium, emphasizing the role of humans and mosquitoes in its transmission and proliferation. Malarial parasites are transmitted as sporozoites to the human body by biting an infected female Anopheles mosquito. These sporozoites then invade liver cells, multiply, and release merozoites, which infect red blood cells, perpetuating the cycle. As this cycle continues, the affected person starts experiencing the clinical symptoms of the disease. The current treatments for malaria, including chloroquine, artemisinin-based combination therapy, and quinine, are discussed alongside the challenges of drug resistance and misdiagnosis. Although efforts have been made to develop a malarial vaccine, they have so far been unsuccessful. Additionally, the review explores the potential of medicinal plants as remedies for malaria, highlighting the efficacy of compounds derived from Artemisia annua, Cinchona species, and Helianthus annuus L., as well as exploration of plants and phytocompounds like cryptolepine, and isoliquiritigenin against drug-resistant Plasmodium species. Moreover, studies from Pakistan further highlight the diverse vegetal resources utilized in malaria treatment, emphasizing the need for further research into natural remedies. Despite the advantages of herbal medicines, including cost-effectiveness, and fewer side effects; their limitations must be taken into account, including variations in potency and potential drug interactions. The review concludes by advocating for a balanced approach to malaria treatment and prevention, emphasizing the importance of early detection, accurate diagnosis, and integrated efforts to combat the disease in the endemic regions.

Pantoea agglomerans: A rare infectious outbreak affecting maintenance hemodialysis patients in a tertiary care hospital.

BACKGROUND: Pantoea agglomerans is an environmental pathogen known to cause infection in immunocompromised individuals, particularly after thorn injuries. However, previous data showed few cases of human disease caused by contaminated medical products such as parenteral nutrition, anesthetic agents, blood, and peritoneal dialysis solutions. Infection in hemodialysis patients is rare. In this study, we presented a detailed account of several hemodialysis patients infected with this contagious pathogen and compared them with noninfected dialysis patients. METHODS: We retrospectively reviewed the hospital records of 105 hemodialysis patients. Seventeen of 105 patients were diagnosed with P. agglomerans infection. We carefully analyzed their entire in-hospital course. RESULTS: Among infected patients, 52.9% were male with a median age of 49 (IQR: 32-66) years. Compared to the noninfected patients, age below 50 years, prior kidney transplantation, prior immunosuppression and antibiotics use, and dialysis via a tunneled vascular catheter were the significant epidemiological features. Despite negative microbiological investigations, we suspect the possible infectious spread via infected central venous catheter was the likely infectious source. Most importantly, all patients responded well to intravenous antibiotics. Only two patients required the removal of the tunneled catheter. Their mortality rate was 0%. CONCLUSION: P. agglomerans infection, although considered rare, is becoming increasingly prevalent among dialysis patients. Its occurrence must be appraised as an infectious outbreak rather than mere contamination. Prompt treatment, source identification, and early implementation of preventive strategies should always be the goal to curtail this infection at an early stage.

To evaluate the utility of Oxford classification in predicting renal outcome in IgA nephropathy patients.

BACKGROUND: Immunoglobulin A Nephropathy (IgAN) is a heterogeneous disorder. Multiple ethnicities conducted studies to assess the effectiveness of the Oxford classification of IgAN in prognostication. However, there is no study on the Pakistani population. We aim to identify its prognostic effectivity in our patients. METHODS: We retrospectively reviewed the medical records of 93 biopsy-proven cases of primary IgAN. We collected the clinical and pathological data at baseline and on follow-ups. The median follow-up period was 12 months. We defined the renal outcome as a ≥ 50% decline in eGFR or end-stage renal disease (ESRD). RESULTS: Of 93 cases, 67.7% were males with a median age of 29. Glomerulosclerosis was the most prevalent lesion (71%). The median MEST-C was 3. On follow-up, median serum creatinine worsened from 1.92 to 2.2 mg/dL, and median proteinuria reduced from 2.3 g/g to 1.072 g/g. The reported renal outcome was 29%. T and C scores and MEST-C scores above 2 were significantly associated with pre-biopsy eGFR. On Kaplan-Meier analysis, the T and C scores' association was significant with the renal outcome (p-value 0.000 and 0.002). In univariate and multivariate analyses, the association of T-score (p-value 0.000, HR 4.691), total MEST-C score (p-value 0.019), and baseline serum creatinine (p-value 0.036, HR 1.188) were significant with the outcome. CONCLUSION: We validate the prognostic significance of the Oxford classification. T and C scores, baseline serum creatinine, and total MEST-C score significantly affect the renal outcome. Furthermore, we recommend the inclusion of the total MEST-C score in determining the IgAN prognosis.

Nutritional composition assessment and antimicrobial activity of Catostylus perezi, jellyfish blooms along the coast of Pakistan: an awareness to avoid food neophobia in Pakistan.

This study highlighted the nutritional importance of Catostylus perezi (an edible jellyfish) in Pakistan; a society where a large proportion of the population suffers from malnutrition, while C. perezi, a blessing of the sea, is wasted or exported. In the present study, the amino acid and fatty acid profiles of the oral arms and umbrella of C. perezi were determined by HPLC. The total amino acid concentration (ΣAA) in the oral arms was 151.19 mg/100g, while in the umbrella it was 100.17 mg/100g. The ratio of total essential amino acids to total non-essential amino acids (TEAA/TNEAA) was 0.72 in the oral arms, while it was 0.70 in the umbrella. Higher amount of ω-3 with lower ratio of ω-6/ω-3 in oral arms (0.52), rather umbrella (ω-6/ω-3 ratio; 0.62). The antimicrobial activity, MIC, MBC, and MFC of the whole body of the edible jellyfish were determined. On the basis of polarity, different solvents were used, e.g. water, methanol, dichloromethane, chloroform, and n-hexane. Among all the extracts, the water extract gave the highest ZOI against C. xerosis (29 mm), while the n-hexane extract gave the lowest ZOI against S. aureus (MRSA) ATCC 33591 (8.20 mm). The water extract of C. perezi had high potential against C. xerosis with the highest AMI and PAI (1.53 and 153, respectively), while the same extract had the highest TAI against E. coli (81.43 mL/g). For fungi/yeast, the methanolic extract had the highest ZOI (29.70 mm) against S. cerevisiae and the lowest MIC/MFC (2.40 µg/mL) against the same pathogen. The n-Hexane extract gave the lowest ZOI (11.10 mm) against P. variotii and the highest MIC/MFC (31.60 µg/mL) against Penicillium sp. Atomic force microscopy (AFM) was used to analyse the disintegrating effect of the extracts (with the highest antimicrobial effect) on the cells of selected Gram-positive, Gram-negative and yeast species. The amino acid and fatty acid profiles and antimicrobial assessment showed that C. perezi has great nutritional importance, so the use of C. perezi as food is highly recommended for the Pakistani community.

Association of neutrophil-to-lymphocyte ratio with clinical, pathological, radiological, laboratory features and disease outcomes of invasive breast cancer patients: A retrospective observational cohort study.

Inflammatory conditions play part in the progression of malignancies, and markers signifying growth of these factors can indicate prognosis. Neutrophil-to-lymphocyte (NLR) is used as a marker of subclinical inflammation that may become an integral part of workup to indicate prognosis and associated pathology. This study aims to explore the association of NLR ratio with clinical characteristics, radiological assessment and staging, histopathology, and disease outcomes of breast cancer. A retrospective cohort study was conducted in a tertiary care center to include breast cancer patients that were diagnosed between January 2001 and December 2020. Data including tumor size, lymph nodes, metastasis, histological grading, ER/PR/HER2-neu status, molecular subtypes, clinical staging); nodal findings (sentinel and axillary); pathology from frozen section; and disease outcomes were assessed. Multivariable regression and Kaplan-Meier survival curves were employed to indicate the association of NLR with breast cancer features and disease-free survival. A total of 2050 patients had a median age of 50 years, median NLR levels of 2.14, most common pathology ductal followed by lobular, and most common site of metastasis being lungs followed by bones. Disease-free rate was 7.6%, and a recurrence rate of 1.8%, while 1.6% deaths were reported. NLR was found associated with age, treatment outcomes, tumor size, lymph nodes, metastasis and clinical staging. Other positive correlations were with Ki67 proliferation index, molecular subtypes, and tumor size on frozen section (at transverse and craniocaudal dimensions). Negative correlations were seen with estrogen and progesterone receptors. However, NLR was not found predictable of disease-free survival (P = .160). Significant predictors of disease-free survival were histological grading, ER, PR status, molecular subtype, and Ki67 proliferation index. NLR being a readily available marker has shown novel findings in its association with tumor staging, disease outcomes and characteristics of breast malignancy.

Administration of sinopharm Covid-19 vaccine in cancer patients.

For prevention against SARS-CoV-2, various vaccines have been approved globally including Pfizer, Sinopharam, Moderna, Johnson & Johnson etc which have proved quite effective. To evaluate the immunization and safety of Sinopharm vaccine in cancer patients. A prospective study was conducted in the Oncology Department of Nishtar Medical Hospital, Multan from March 2021- September 2021. A total of 150 cancer patients undergoing treatment were included in the study. All the patients were administered 0.5 ml Sinopharm vaccine with 28 day difference between the two doses. A two-month follow-up was done to test the immunization using ELISA kits. Among all the patients, 16 patients (10.7%) had a history of COVID-19 before the administration of the vaccine. At the time of vaccination, 23.3% of patients were seropositive. After the vaccination, 130 patients (86.7%) developed immunity against the infection. 30.6% of participants developed a fever and 20.9% had fatigue. Other side effects were also observed including pain, redness, swelling, itching, chills, anorexia, nausea, vomiting, myalgia and diarrhea. Sinopharm vaccine is effective and safe for patients with malignancies especially in patients receiving radiaton therapy but still recommended for older patients and patients receiving chemotherapy.

Incidence of COVID-19 and Identification of Possible Risk Factors Associated with COVID-19 in Acute Renal Transplant Recipients in Pakistan.

BACKGROUND Renal transplant recipients are susceptible to increased mortality with COVID-19 infection. There is insufficient data regarding risk factors for COVID-19 disease acquisition. We aimed to identify them here. MATERIAL AND METHODS We enrolled Pakistani renal transplant recipients from February 10, 2020, to March 18, 2021, and actively tracked their baseline health status, transplant characteristics, comorbidities, immunosuppressive therapies, and post-transplant follow-ups until September 2021. Furthermore, we formulated 2 questionnaires for their compliance assessment with COVID-19-preventive measures. We also identified COVID-19 disease acquisition, symptomatology, and management. RESULTS Among the 50 enrolled patients, 14 (28%) patients developed COVID-19, which is higher than the incidence observed in general Pakistani population (0.55%). Their mean age was 35.38 years ±11.69 SD years, and 82% of patients were males. The following factors were independently associated with COVID-19 disease: female gender (P value: 0.042), diabetes mellitus (P value: 0.002), anti-thymocyte globulin (ATG) induction (P value: 0.006), in-person follow-ups (P value: 0.000), prolonged immediate and late post-transplant hospital stays (P value: 0.019 and 0.000, respectively), raised post-transplant serum creatinine (P value: 0.019), and COVID-19 protective measures non-compliance (P value: 0.000). Out of 14 infected recipients, 92.85% required symptomatic management and overall mortality was 0%. CONCLUSIONS Female gender, diabetes mellitus, ATG induction, in-person follow-ups, prolonged hospital stays, raised post-transplant serum creatinine, and COVID-19-protective measures non-compliance were associated with the higher acquisition of SARS-CoV-2 infection. By taking concrete measures against these risk factors, we can continue renal transplants, as overall mortality was lower than in the general Pakistani population (2%).

Anti-Phospholipase A2 Receptor Antibodies in Biopsy-Proven Idiopathic Membranous Nephropathy: A Report from the Pakistani Population.

This study aimed to determine the percentage of anti-phospholipase A2 receptor (PLA2R) autoantibody positivity in a cross-section of 74 Pakistani patients with biopsy-proven idiopathic membranous nephropathy. It was an observational study conducted from December 2018 to June 2019. Seventy-four (n=74) consecutive biopsy-proven cases of membranous nephropathy, aged between 12-60 years, were included. Out of them, 63.5% (n=47) were males and 36.5% (n=27) were females. The mean age was 40.2±16.7 years. Anti-PLA2R antibodies were positive in 35 (47.3%) patients, negative in 38 (51.4%) patients, and borderline positive in 1(1.35%) patient. A significant difference (p ≤ 0.05) was noted among different levels of antibodies in both genders. Anti-PLA2R antibodies were detected in approximately half of the diagnosed idiopathic membranous nephropathy cases. However, this percentage was much lower than the studies conducted on other populations around the globe, indicating a possible pathogenic role of other antigens in our population. Key Words: Membranous nephropathy, Phospholipase A2 receptors, Renal biopsy.

Dramatic Response of Lupus Enteritis, Nephritis, and Pancytopenia to Plasmapheresis and Rituximab.

Background: Although lupus enteritis is a rare manifestation of systemic lupus erythematosus yet results in significant distress. This disorder contributes to diagnostic and therapeutic dilemma leading to enhanced mortality. Case Description. We report a case history of a 29-year-old female who presented with severe abdominal pain, watery stools, and vomiting, and later on, she developed pancytopenia and renal impairment. On intensive workup, diagnosis of lupus-associated enteritis, nephritis, and pancytopenia was discovered. She improved drastically on initiation of plasmapheresis followed by low-dose intravenous rituximab. One year posttreatment, she remained in complete remission. Conclusion: From this case, it can be suggested that in a young female with intractable abdominal pain, the remote possibility of lupus enteritis must be kept in mind. Besides this, plasmapheresis can have a potential role in refractory lupus enteritis. Furthermore, low-dose intravenous rituximab can be a safe and cost-effective treatment option in achieving sustained remission of clinical and laboratory parameters in lupus enteritis.

Granulomatous Disorder With Pulmonary and Renal Involvement: A Diagnostic and Therapeutic Dilemma.

Granulomatosis with polyangiitis (GPA) can present with a wide array of clinical signs and symptoms; therefore, it should be differentiated from other mimicking clinicopathological entities. We report a case of a 66-year-old gentleman who was found to have a mediastinal mass and histopathological examination showed chronic necrotizing granulomatous inflammation. The patient was managed on lines of pulmonary tuberculosis for 12 months and remained in remission for two years. Later, workup showed cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA)-associated granuloma with marked renal impairment, which responded to immunosuppression. From this, we suggest that in a patient with radiological evidence of mediastinal mass, the remote possibility of GPA must be kept in mind.

Coexistence of Lupus Nephritis, Ulcerative Colitis, and Communicating Hydrocephalus: A Report of a 21-Year-Old Male.

Systemic lupus erythematosus (SLE) and ulcerative colitis (UC) are multisystem autoimmune disorders that rarely coexist. We report a case history of a 21-year-old male, presenting with bloody diarrhea and, later, diagnosed to have ulcerative colitis on colonic biopsy. There was clinically silent renal impairment leading to end-stage kidney disease requiring hemodialysis possibly secondary to ongoing lupus nephritis as suggested by positive lupus-specific antibodies' detection. Besides this, the diagnosis of lupus associated with early communicating hydrocephalus was made on CT brain findings which clinically responded well to the initiation of immunosuppressive therapy. It is imperative to keep in mind the remote possibility of ulcerative colitis in an SLE patient with gastrointestinal (GI) manifestations. Communicating hydrocephalus is a rare neurological manifestation of SLE leading to seizures and can respond well to the initiation of steroids and immunosuppressants. Therefore, a trial of immunosuppressant medications must be given even in a patient with end-stage renal disease (ESRD) to halter extra renal rare lupus manifestations.

Molecular histocompatibility beyond Tears: The next generation version.

Human Leukocyte Antigens (HLA) matching at the serological level used to serve as the measure of histocompatibility between organ donors and recipients. With advancements in HLA typing methods more precise HLA mismatch assessment tools were developed to measure dissimilarities at the molecular level, collectively referred to as Molecular Mismatch load analysis tools. Currently, several software are aimed at deciphering the dissimilarities using somewhat different immunologic rationales. Our goal, in this review is to provide a basic overview of the different computational approaches, provide clinical cases to contextualize concerns regarding the lack of assessment of immunogenicity, and present our personal view regarding the gaps and the needs of our field.

Analysis of Clinical, Pathological and Prognostic Features of Coexistent Membranous and IgA Nephropathy in a Series of 13 Patients at a Tertiary Care Hospital.

Background Membranous nephropathy (MN) and immunoglobulin A nephropathy (IgAN) are although two different entities, yet can rarely coexist. There is not much data available on this coexistent disorder, specifically with regard to the treatment modality and outcome. Here, we analyse in detail, retrospectively, 13 cases of coexistent IgA and membranous nephropathy (IgA-MN). Methods Renal biopsy data of 1084 diagnosed cases of either membranous or IgA nephropathy was obtained from March 2015 till March 2021. Out of 1084 patients, 19 diagnosed cases of the coexistent disorder were identified. Six out of 19 patients were excluded because of their unwillingness. From remaining 13 patients, data regarding clinical presentation, investigations, management and treatment response was collected from hospital database, files and via telephonic interview. Results The overall prevalence noted was 1.75%. Among them, 53.8% were females and 46.2% were males. Their median age was 40 years (range: 14-71 years). On workup, mean serum albumin was 2.64 g/dl (range: 1.6-3.8 g/dl), mean proteinuria was 5.5 g/24 hours (range: 1.55-11.48 g/24 hours) and mean creatinine was 0.98 mg/dl (range: 0.5-2.8 mg/dl). Anti-phospholipase A2 receptor antibody positivity was only 14.2%. The renal biopsy of all patients showed thickening of the glomerular basement membrane with granular IgG deposits and mesangial expansion with granular IgA deposits. A total of 80% patients showed complete remission with steroids, calcineurin inhibitors (CNIs) and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs). Conclusion IgA-MN is probably a separate disorder that can only be confirmed on immunofluorescence microscopy. The response to the combination of steroids, CNIs and ACEi/ARBs is found to be the most effective; hence, this combination must often be used for the management of this coexistent disorder.

Association of Adult-Onset Bartter Syndrome With Undifferentiated Connective Tissue Disorder.

Bartter syndrome is a rare autosomal recessive, salt-losing disorder characterized by hypokalemic hypochloremic metabolic alkalosis. We are reporting a case of 21 years old patient, who presented with lower limb weakness, marked hypokalemia, proteinuria, and renal impairment detected on laboratory evaluation. The diagnosis of Bartter syndrome was suspected by marked hypokalemia and was supported by renal biopsy which showed evidence of Juxtaglomerular (JG) hyperplasia. This is the first case report about clinicopathological features of the patient with acquired Bartter syndrome and associated undifferentiated connective tissue disorder manifesting as hypokalemia with paralysis.

Clinical Interpretation of Detection of IgM Anti-Brucella Antibody in the Absence of IgG and Vice Versa; a Diagnostic Challenge for Clinicians.

Non-specific and often misleading clinical presentation of active brucellosis has made it a diagnostic puzzle for treating physicians. Clinicians rely greatly on the detection of IgG and IgM anti-Brucella antibodies by ELISA. Different patterns of positivity have been observed for IgG and IgM anti-Brucella antibodies in different cases, which further increases the risk of an erroneous diagnosis. Detailed herein is our two-years data with varied Brucella serology patterns and their clinical interpretation. Between January 2015 to December 2017, 1102 samples were processed in the Immunology Laboratory of KFHU for Brucella serology. 68 samples were positive for both IgG and IgM, 28 samples were positive for IgG and negative for IgM while 15 samples were positive for IgM and negative for IgG antibodies against Brucella. Electronic medical records, history of exposure, signs, symptoms, laboratory data, and the final diagnosis were recorded for all these patients. None of the patients with only positive IgM antibodies was finally diagnosed with brucellosis, while a diagnosis of brucellosis was established for only one patient with IgG antibodies positive in his serum. All the double-positive (IgG- and IgM-positive) serology patterns were diagnosed as having brucellosis. We concluded that determination of single IgM or IgG anti-Brucella-antibodies by ELISA could both be considered as definite and should ideally be interpreted in the context of appropriate clinical scenario and confirmation by other laboratory assays.Non-specific and often misleading clinical presentation of active brucellosis has made it a diagnostic puzzle for treating physicians. Clinicians rely greatly on the detection of IgG and IgM anti-Brucella antibodies by ELISA. Different patterns of positivity have been observed for IgG and IgM anti-Brucella antibodies in different cases, which further increases the risk of an erroneous diagnosis. Detailed herein is our two-years data with varied Brucella serology patterns and their clinical interpretation. Between January 2015 to December 2017, 1102 samples were processed in the Immunology Laboratory of KFHU for Brucella serology. 68 samples were positive for both IgG and IgM, 28 samples were positive for IgG and negative for IgM while 15 samples were positive for IgM and negative for IgG antibodies against Brucella. Electronic medical records, history of exposure, signs, symptoms, laboratory data, and the final diagnosis were recorded for all these patients. None of the patients with only positive IgM antibodies was finally diagnosed with brucellosis, while a diagnosis of brucellosis was established for only one patient with IgG antibodies positive in his serum. All the double-positive (IgG- and IgM-positive) serology patterns were diagnosed as having brucellosis. We concluded that determination of single IgM or IgG anti-Brucella-antibodies by ELISA could both be considered as definite and should ideally be interpreted in the context of appropriate clinical scenario and confirmation by other laboratory assays.

Skin Prick Test Reactivity to Common Aeroallergens among Allergic Rhinitis Patients.

OBJECTIVE: To identify the common aeroallergens causing allergy symptoms among the allergic rhinitis patients. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Immunology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from January to July 2016. METHODOLOGY: Patients with a clinical diagnosis of allergic rhinitis were enrolled. Skin Prick Test (SPT) was performed on these patients using 12 common aeroallergens along with positive (histamine hydrochloride, 10 mg/ml) and negative (glycerin saline) controls. Results were recorded after 15 minutes, considering a wheal diameter >3 mm as positive. Chi-square test was used to compare frequencies; and p-value of less than 0.05 was considered significant. RESULTS: Out of 130 patients, 78 (60%) were males and 52 (40%) were females. The rate of sensitization to any allergen was 90%. One hundred and two (78%) were poly-sensitized to more than two allergens and 20% were sensitized to more than six allergens. Most common outdoor and indoor allergens were Broussonetia papyrifera (50.7%) and Dermatophagoides farina (42.3%), respectively. Dog epithelia and aspergillus were the least prevalent allergens (13.8% each). CONCLUSION: This study highlighted an increased overall frequency of sensitization to any allergen and significance of tree and weed allergens; especially, Broussonetia papyrifera and Cannabis sativa. It also emphasized increased prevalence of skin reactivity to indoor allergen, Dermatophagoides farina in the city.

T cell reactivity to Collagen II as a possible prognostic marker in patients with rheumatoid arthritis.

OBJECTIVE: To compare the frequency and the functional state of the collagen II reactive T cells with disease activity in rheumatoid arthritis patients and healthy controls. METHODS: This case-control cross-sectional study was carried out at the Department of Immunology; Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from June to October 2014. Rheumatologist from Rehmat Noor Rheumatology Clinic, a private health facility of the city, was requested to send in patients with clinical diagnosis of rheumatoid arthritis. Samples were obtained and relevant investigations were carried out. Data were compared with a group of age and gender-matched healthy subjects. T cell proliferative response was assessed against bovine collagen II by measuring incorporation of bromodeoxyuridine into deoxyribonucleic acid of proliferating cells and by expression of CD25 on proliferating cells as percentage of CD3+/bromodeoxyuridine+ and CD3+/CD25+ T-cells, respectively. Among the patients, the frequency of T cells with disease activity was compared. Patients were classified into groups of mild, moderate and severe disease and frequency of CD3+/bromodeoxyuridine+, frequency of CD3+/CD25+ cells, mean fluorescent intensity of bromodeoxyuridine-fluorescein isothiocyanate and mean fluorescent intensity of CD25-fluorescein isothiocyanate were compared in the groups. RESULTS: Of the 60 subjects, 30(50%)were patients and 30(50%) were controls. Of the patients, 5(16.66%) were males and 25(83.33%) were females with an overall mean age of 42±12 years. The mean age of the controls was 41±9.28 years. Mean disease duration of the patients was 10.5 ± 4.2 years. Percentage of CD3+/CD25+ cells and CD3+/bromodeoxyuridine+ cells stimulated with collagen II, in patients was much higher than the controls(p<0.05).Statistically significant differences were observed when frequency of CD3+/bromodeoxyuridine+ cells and CD3+/CD25+ cells was compared among the mild, moderate and severe patient groups (p<0.05). CONCLUSIONS: Collagen II was found to be an important auto antigen in joints of rheumatoid arthritis patients.

Short term exposure to titanium, aluminum and vanadium (Ti 6Al 4V) alloy powder drastically affects behavior and antioxidant metabolites in vital organs of male albino mice.

Titanium, Aluminum and Vanadium (Ti 6Al 4V) alloy are frequently used as surgical implant but regarding their compatibility in living systems is limited. Ti 6Al 4V was prepared from high purity constituents and Ti 6Al 4V alloy powder (25 mg/ml solvent/Kg body weight) was gavaged to albino mice for 8 days. A saline treated control group was maintained in parallel. A series of behavioral (rota rod, light and dark box, open field and novel object) test performance, complete blood count, selected serum (HDL cholesterol, LDL cholesterol, creatinine, cholesterol and triglycerides) parameters, antioxidant metabolites from vital organs (superoxide dismutase, catalase and lipid peroxidation) from vital organs and body weight were determined in both treatments. It was observed that rota rod test performance in male (P = 0.05) and novel object recognition capability in female mice (P = 0.04) were significantly reduced as compared to their respective control groups. Body weight, complete blood count and studied serum parameters remained unaffected when compared between two treatments of both genders. Concentration of superoxide dismutase in liver (P = 0.008), heart (P = 0.01) and lungs (P = 0.05) was significantly elevated while catalase concentration in liver (P = 0.001) was significantly decreased in female albino mice that were exposed to 25 mg/ml solvent/kg body weight of Ti 6 A l 4 V alloy powder. In case of male albino mice, superoxide dismutase concentration in lungs was reduced (P = 0.05) in mice exposed to Ti 6 A l 4 V alloy powder. In conclusion, our results indicated that short term exposure to 25 mg/ml solvent/Kg body weight of Ti-6Al-4V alloy powder supplementation had adversely affected selected aspects of behavior of albino mice in a gender specific manner. Analysis of antioxidant parameters in vital organs has demonstrated that the applied dose of Ti-6Al-4V alloy powder can disturb the H2O2 associated metabolic pathways in albino mice, especially in female mice. As this alloy is part of surgical implants, so we recommend that their effects in living systems must be extensively explored under variable dose and exposure time conditions to know more about their biocompatibility.