Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs

Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.     

Assessment of heavy metals by ICP-OES and their impact on insulin stimulating hormone and carbohydrate metabolizing enzymes

Arsenic (As) and cadmium (Cd) have recently emerged as major health concerns owing to their strong association with diabetes mellitus (DM). We aimed to investigate the heavy metals exposure towards incidence of DM at various enzymatic and hormonal levels. Additionally, association of As and Cd with Zinc (Zn, essential metal) was also evaluated. Spot urine samples were collected to assess As, Cd and Zn through ICP-OES. Serum was analyzed by assay method for fasting blood glucose, liver and renal function biomarkers. ELISA was performed to investigate the impact of heavy metals on HbA1c, α-amylase, DPP-IV, IGF-1, leptin, GSH, MDA, SOD, HDL, FFA, TG and interleukin (IL)-6. Association of heavy metals with DM was measured by odds ratio (OR) and level of significance was assessed by Chi-squared test. Unpaired student's t-test was used to compare DM-associated risk factors in heavy metals-exposed and unexposed participants. As and Cd were detectable in 75.4% and 83% participants with mean concentration of 75.5 ppb and 54.5 ppb, respectively. For As exposure, OR in the third quartile was maximum ie 1.34 (95% CI, 0.80 to 2.23), however the result was not statistically significant (P > .05). For Cd exposure, OR in the fourth quartile was considerably high, 1.62 (95% CI, 1.00 to 2.61), with a significant probability value (P < .05). Urinary Cd was negatively associated with Zn. As and Cd exposure increases the incidence of DM in the general population. Impaired hormonal and enzymatic levels in diabetic and non-diabetic exposed participants reflect the multiple organ damage by heavy metal exposure.     

Stage 1 acute kidney injury is independently associated with infection following cardiac surgery

ObjectivesSevere acute kidney injury (AKI) is a known risk factor for infection and mortality. However, whether stage 1 AKI is a risk factor for infection has not been evaluated in adults. We hypothesized that stage 1 AKI following cardiac surgery would independently associate with infection and mortality.MethodsIn this retrospective propensity score–matched study, we evaluated 1620 adult patients who underwent nonemergent cardiac surgery at the University of Colorado Hospital from 2011 to 2017. Patients who developed stage 1 AKI by Kidney Disease Improving Global Outcomes creatinine criteria within 72 hours of surgery were matched to patients who did not develop AKI. The primary outcome was an infection, defined as a new surgical-site infection, positive blood or urine culture, or development of pneumonia. Secondary outcomes included in-hospital mortality, stroke, and intensive care unit (ICU) and hospital length of stay (LOS).ResultsStage 1 AKI occurred in 293 patients (18.3%). Infection occurred in 20.9% of patients with stage 1 AKI compared with 8.1% in the no-AKI group (P < .001). In propensity-score matched analysis, stage 1 AKI independently associated with increased infection (odds ratio [OR]; 2.24, 95% confidence interval [CI], 1.37-3.17), ICU LOS (OR, 2.38; 95% CI, 1.71–3.31), and hospital LOS (OR, 1.30; 95% CI, 1.17-1.45).ConclusionsStage 1 AKI is independently associated with postoperative infection, ICU LOS, and hospital LOS. Treatment strategies focused on prevention, early recognition, and optimal medical management of AKI may decrease significant postoperative morbidity.     

Xanthogranulomatous orchitis: Review of the published work and report of one case

Xanthogranulomatous orchitis is an extremely rare inflammatory non-neoplastic destructive lesion of the testis. We report a 44-year-old man who presented with right scrotal swelling and two discharging sinuses. Testicular tumor markers were normal. Scrotal ultrasound showed heterogeneous testicular areas and irregular margin of the tunica. Surgical exploration revealed infected, unhealthy testicular tissue with necrosis and tumor-like lesion. Orchidectomy was done and histopathology showed xanthogranulomatous orchitis.     

Management of liver injuries in Zaria, Nigeria

The records of 37 patients with liver injuries operated upon at the Ahmadu Bello University Teaching Hospital, Zaria, Nigeria from 1976 to 1987 were reviewed. There were 31 males and 6 females with a mean age of 22 years. Sixty-two per cent were due to blunt injury from road traffic accidents, 14 per cent were due to gunshot wounds and 5 per cent due to stab wounds as a result of assaults. Treatment with simple suture and drainage sufficed in 49 per cent; only 16 per cent required resection, packing and drainage. Associated injuries included long bone fractures and chest trauma. The most common complication was sepsis and the overall mortality was 19 per cent.     

Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics.

BACKGROUND: A subgroup of children with obsessive-compulsive and tic disorders are proposed to have an infectious trigger. The purpose of this study was to investigate the relationship between group A streptococcal titers and symptom fluctuations in children with a clinical course resembling that described for pediatric autoimmune neuropsychiatric disorders associated with streptococcus. METHODS: Twenty-five children with obsessive-compulsive disorder and/or tic disorder were evaluated for neuropsychiatric severity and group A streptococcal antibody titers (streptolysin O, deoxyribonuclease B, and carbohydrate A) at 6-week intervals for > or = six consecutive evaluations (total visits=277). RESULTS: Children with large symptom fluctuations (n=15) were compared with children without dramatic fluctuations (n=10). Co-movements of obsessive-compulsive/tic severity and group A streptococcal antibodies were assessed. In subjects with large symptom changes, positive correlations were found between streptococcal titers and obsessive-compulsive severity rating changes (p=.0130). These subjects were also more likely to have elevated group A streptococcal titers during the majority of observations (p=.001). Tic symptom exacerbations occurred more often in the fall/winter months than spring/summer months (p=.03). CONCLUSIONS: Patients with marked obsessive-compulsive/tic symptom changes may be characterized by streptococcal titer elevations and exhibit evidence of seasonal tic exacerbations.     

Schwannoma of submandibular region

Tumours of the nerve sheath origin in the head and neck are not common. Schwannomas are rare. Only a few cases have been reported so far. We report a rare case of Schwannoma of Submandibular region arising from the lingual nerve.     

Lipophilic platinum complexes entrapped in liposomes: improved stability and preserved antitumor activity with complexes containing linear alkyl carboxylato leaving groups

Lipophilic diaminocyclohexane (DACH) platinum complexes have shown significant promise in preclinical studies. One of these compounds,cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexaneplatinum(II) (NDDP), which contains two branched leaving groups of 10 carbons, showed a favorable toxicity profile in a liposomal formulation in early clinical trials. However, like many other DACH platinum compounds with branched leaving groups, it is unstable within the liposomes, thus preventing its widespread clinical evaluation. We studied the effect of the configuration of leaving groups on intraliposomal complex stability by studying a series of DACH platinum complexes containing linear alkyl carboxylato leaving groups of 5–18 carbons. The entrapment efficiency was greater than 90% for all liposomal preparations of the complexes and was independent of lipid composition and length of the leaving group. The drug leakage from the liposomes was minimal, but was directly related to the length of the leaving group. Intraliposomal stability was inversely related to the length of the leaving group and the content of DMPG (dimyristoyl phosphatidylglycerol) in the liposomes. The effect of length of leaving group on intraliposomal stability was minimal in compounds with leaving groups smaller than 10 carbons, but very pronounced in compounds with longer leaving groups. Stable liposomal formulations of selected compounds with leaving groups of 6 and 10 carbons had significant in vivo antitumor activity against both L1210/S and L1210/PDD leukemias. The results indicate (1) that compounds with linear leaving groups are much more stable within DMPG-containing liposomes than compounds with branched leaving groups and (2) that DMPG is required for in vivo antitumor activity. Stable and active liposomal formulations of selected compounds with linear leaving groups have been identified. These formulations are candidates for clinical development.Abbreviations DMPC dimyristoyl phosphatidylcholine - DMPG dimyristoyl phosphatidylglycerol - L-NDDP liposomalcis-bis-neodecanoato-trans-1,2-diaminocyclohexaneplatinum(II) The work reported in this paper was supported in part by NIH grants CA 41581, 45423, 50270, and 58342