IL-6 levels decrease with SSRI treatment in patients with major depression

OBJECTIVE: Some evidence indicates that an immune response with an increased production of proinflammatory cytokines often accompanies major depression. The objective of this study was to examine the serum levels of IL-6 in patients with major depression and the changes occurring in IL-6 levels during treatment with selective serotonin reuptake inhibitors (SSRI). METHOD: Twenty-three patients with a DSM-IV diagnosis of major depressive disorder and 23 healthy matched controls were included in the study. The severity of depression was measured with the Hamilton rating scale for depression. Blood samples for IL-6 levels were obtained at baseline and at week 6 of treatment and IL-6 concentrations were evaluated using a solid phase sandwich enzyme immunoassay. All patients were treated with an SSRI. RESULTS: The IL-6 levels showed no statistically significant difference between the patients and the controls at baseline. However, IL-6 levels after treatment with SSRIs were significantly lower compared with the baseline IL-6 levels of both the patients and the controls. CONCLUSION: The results of this study suggest that proinflammatory cytokines show some changes during the course of treatment of major depression. These findings might also be considered as supporting the hypothesis of a modulatory role of antidepressants on the immune system.     

High expression of transforming growth factor-beta long cell cycle times and a unique clustering of S-phase cells in patients with acute promyelocytic leukemia.

Expression of transforming growth factor-beta (TGF-beta), which inhibits the proliferation of hematopoietic progenitors, was investigated simultaneously with cell cycle characteristics in 63 bone marrow biopsies from 23 cases with acute promyelocytic leukemia (APL). Bromodeoxyuridine (BrdU) was administered to every patient (17 newly diagnosed) for determination of the labeling index (LI) and the durations of S-phase (Ts) and the cell cycle (Tc) of leukemic promyelocytes. APL cases had lower LI both in the bone marrow aspirate (6.1% v 11.4%, P = .008) and biopsy (21.1% v 28.0%, P = .001) and longer Tc (93.6 hours v 56.0 hours, P = .002) when compared with other French-American-British subtypes. TGF-beta expression (detected by a monoclonal anti-TGF-beta 2/beta 3 antibody) was dramatically high, especially in interstitial areas of the biopsies. S-phase cells were found as geographically restricted islands of proliferation (GRIPs) in 20 of 22 cases. Weekly biopsies showed an increment in TGF-beta on day 7 of therapy in 13 of 17 cases, while in vivo differentiation was noted in 9 of 15. We conclude that the presence of high TGF-beta expression may explain the biologic basis for the slowly cycling nature of leukemic promyelocytes in APL as well as the unique clustering of S-phase cells observed in GRIPs.     

Coactivating signals for the hepatic lymphocyte gamma interferon response to Francisella tularensis

The facultative intracellular bacterium Francisella tularensis is capable of causing systemic infections in various hosts, including mice and humans. The liver is a major secondary site of F. tularensis infection, but hepatic immune responses to the pathogen remain poorly defined. Immune protection against the pathogen is thought to depend on the cytokine gamma interferon (IFN-gamma), but the cellular basis for this response has not been characterized. Here we report that natural killer cells from the livers of na?ve uninfected mice produced IFN-gamma when challenged with live bacteria in vitro and that the responses were greatly increased by coactivation of the cells with either recombinant interleukin-12 (IL-12) or IL-18. Moreover, the two cytokines had strong synergistic effects on IFN-gamma induction. Neutralizing antibodies to either IL-12 or IL-18 inhibited IFN-gamma production in vitro, and mice deficient in the p35 subunit of IL-12 failed to show IFN-gamma responses to bacterial challenge either in vitro or in vivo. Clinical isolates of highly virulent type A Francisella tularensis subsp. tularensis organisms were comparable to the live attenuated vaccine strain of Francisella tularensis subsp. holarctica in their ability to induce IL-12 and IFN-gamma expression. These findings demonstrate that cells capable of mounting IFN-gamma responses to F. tularensis are resident within the livers of uninfected mice and depend on coactivation by IL-12 and IL-18 for optimum responses.     

Clinical characteristics and predictors of progression of chronic kidney disease in autosomal dominant polycystic kidney disease: a single center experience

Background

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease. The course and progression of the disease is highly variable. In this study, we aimed to investigate the impact of clinical characteristics and basic biochemical parameters on progression of chronic kidney disease (CKD) in ADPKD patients.

Materials and methods

A total of 323 consecutive patients with ADPKD were enrolled into the study and followed with a mean duration of 100 ± 38 months. Patients were grouped as rapid progressors (RP) and slow progressors (SP) according to median rates of decline in glomerular filtration rate (ΔGFR) per year, namely 1 ml/min/year.

Results

History of macroscopic hematuria, urinary stone and smoking were more common in male patients; hepatic and other organ cysts were more common in female patients. ?GFR/year was similar between males and females [0.95 (0–3.02) vs. 1.11 (0.10–2.74) ml/min/year, p = 0.21]. History of smoking and pack-year of cigarettes smoked were significantly higher in the RP compared to the SP group (36 vs. 18 %, p = 0.01 and 5.24 ± 1.20 vs. 3 ± 1.32 pack-year, p = 0.02, respectively). Baseline 24 h-proteinuria was found to be significantly correlated with the percent decline of GFR (?%GFR) per year (r = 0.303, 0.001). In Cox regression analysis for predicting the progression of CKD, age, hypertension, urinary stone and proteinuria were retained as the significant independent factors predicting progression of CKD in the model.

Conclusion

Baseline proteinuria was significantly correlated with ?%GFR per year. Hypertension and proteinuria were found to be the major treatable risk factors for the progression of CKD in ADPKD patients.     

Plerixafor for PBSC mobilisation in myeloma patients with advanced renal failure: safety and efficacy data in a series of 21 patients from Europe and the USA

We describe 20 patients with myeloma and 1 with primary amyloidosis from 15 centres, all with advanced renal failure, most of whom had PBSC mobilised using plerixafor following previous failed mobilisation by conventional means (plerixafor used up-front for 4 patients). For 15 patients, the plerixafor dose was reduced to 0.16?mg/kg/day, with a subsequent dose increase in one case to 0.24?mg/kg/day. The remaining six patients received a standard plerixafor dosage at 0.24?mg/kg/day. Scheduling of plerixafor and apheresis around dialysis was generally straightforward. Following plerixafor administration, all patients underwent apheresis. A median CD34+ cell dose of 4.6 × 10(6) per kg was achieved after 1 (n=7), 2 (n=10), 3 (n=3) or 4 (n=1) aphereses. Only one patient failed to achieve a sufficient cell dose for transplant: she subsequently underwent delayed re-mobilisation using G-CSF with plerixafor 0.24?mg/kg/day, resulting in a CD34+ cell dose of 2.12 × 10(6)/kg. Sixteen patients experienced no plerixafor toxicities; five had mild-to-moderate gastrointestinal symptoms that did not prevent apheresis. Fifteen patients have progressed to autologous transplant, of whom 12 remain alive without disease progression. Two patients recovered endogenous renal function post autograft, and a third underwent successful renal transplantation. Plerixafor is highly effective in mobilising PBSC in this difficult patient group.     

Diagnosis of cardiac sarcoidosis: an era of paradigm shift

Cardiac sarcoidosis is a granulomatous disease that may affect any organ, including the heart. Diagnosis of cardiac sarcoidosis is challenging, given the varied and non-specific clinical presentation and limited sensitivity and specificity of available diagnostic tests. With the growing interest and developments in imaging techniques, cardiac magnetic resonance imaging (CMR) and positron emission tomography (PET) have emerged as important tools in the diagnostic evaluation of patients with suspected cardiac sarcoidosis. These modalities have been given increasing emphasis in successive published diagnostic guidelines for CS. This review will provide an update on the recent paradigm shift in diagnostic guidelines for cardiac sarcoidosis, with a focus on the advanced cardiac imaging modalities and their developed role in clinical practice.     

Exploration of Nutraceutical Potential of Herbal Oil Formulated from Parasitic Plant

Background

Cuscuta reflexa (C. reflexa) is a parasitic climber of medicinal importance. The present study was aimed to evaluate the nutraceutical potential of C. reflexa stems collected from different hosts and to evaluate the role of the herbal formulation in dandruff, hair fall control as well as hair growth promoter.

Materials and Methods

Hair formulations of C. reflexa collected from different host plants were prepared in the form of herbal oils (10% w/v). C. reflexa stems were extracted using mustard oil as base oil by using direct boiling technique. Prepared oil was studied as hair tonic. The experimental protocols used were anti-dandruff hair growth activity, as well as hair fall reduction. Herbal hair oils versus mustard oil were evaluated by applying oils on human volunteers with hair fall and dandruff problem whereas promotion of hair growth activity was conducted on rats. The formulated oils were also characterised for proximate analysis, physiochemical composition, as well as antimicrobial activity.

Result

The test oils of C. reflexa collected from Azadiracta indica and Zizyphus jujuba were effective in the promotion of hair growth, dandruff control, as well as reduction in hair fall activity.

Conclusion

All the formulated oils showed potent antimicrobial activity against all selected strains of bacteria and fungi.