The broad effects of the functional IL-10 promoter-592 polymorphism: modulation of IL-10, TIMP-3, and OPG expression and their association with periodontal disease outcome

Periodontal diseases are infectious diseases, in which periodontopathogens trigger chronic inflammatory and immune responses that lead to tissue destruction. It occurs through the generation of metalloproteinases and the activation of bone resorption mechanisms. Anti-inflammatory cytokines such as IL-10 seem to attenuate periodontal tissue destruction through the induction of tissue inhibitors of metalloproteinases (TIMPs) and the inhibitor of osteoclastogenesis osteoprotegerin (OPG). A high individual variation in levels of IL-10 mRNA is verified in periodontitis patients, which is possibly determined by genetic polymorphisms. In this study, the IL-10 promoter -592C/A single nucleotide polymorphism (SNP), which is associated with a decrease in IL-10 production, was analyzed by RFLP in 116 chronic periodontitis (CP) patients and 173 control (C) subjects, and the IL-10, TIMPs, and OPG mRNA expression levels in diseased gingival tissues were determined by real-time-PCR. The IL-10-592 SNP CA (P=0.0012/OR=2.4/CI:1.4-4.1), AA (P=0.0458/OR=2.3/CI:1.1-4.9), and CA+AA (P=0.0006/OR=2.4/CI:1.4-3.4) genotypes and the allele A (P=0.0036/OR=1.7/CI:1.2-2.4) were found to be significantly more prevalent in the CP group when compared with control subjects. Both CA and AA genotypes were associated with lower levels of IL-10, TIMP-3, and OPG mRNA expression in diseased periodontal tissues and were also associated with disease severity as mean pocket depth. Taken together, the results presented here demonstrate that IL10-592 SNP is functional in CP, being associated with lower levels of IL-10 mRNA expression, which is supposed to consequently decrease the expression of the downstream genes TIMP-3 and OPG, and influence periodontal disease outcome.     

Activation pattern of neutrophils from blood of elderly individuals with Candida-related denture stomatitis

We have identified impaired neutrophils in elderly individuals which could be involved with Candida-related denture stomatitis (DS), an oral infection predominantly caused by Candida albicans, affecting especially elderly individuals using dental prosthesis. However, specific mechanisms performed by neutrophil contributing to the susceptibility of the elderly to DS are not fully understood. This study evaluated activation features of blood neutrophils from elderly and young individuals with DS. Blood neutrophils cultured with C. albicans from elderly subjects secreted decreased levels of CXCL8. However, C. albicans challenged-neutrophils from DS patients produced high IL-4 and IL-10, and low GM-CSF levels, regardless of age. Additional elastase activity of neutrophils from both elderly groups was detected after incubation with C. albicans, but only neutrophils from elderly DS demonstrated high myeloperoxidase activity. Therefore, DS patients have affected neutrophils, and the advance of age intensifies these damages. In sumamry, individuals with Candida-related denture stomatitis presented variation in the neutrophil phenotype and activation. Such alterations were more intense in neutrophils from infected elderly individuals.     

ICV-transplanted human glial precursor cells are short-lived yet exert immunomodulatory effects in mice with EAE

Human glial precursor cells (hGPs) have potential for remyelinating lesions and are an attractive cell source for cell therapy of multiple sclerosis (MS). To investigate whether transplanted hGPs can affect the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, we evaluated the therapeutic effects of transplanted hGPs together with the in vivo fate of these cells using magnetic resonance imaging (MRI) and bioluminescence imaging (BLI). At 14 days post-EAE induction, mice (n = 19) were intracerebroventricularly (ICV) injected with 5 × 10(5) hGPs that were magnetically labeled with superparamagnetic iron oxide (SPIO) particles as MR contrast agent and transduced with firefly luciferase for BLI of cell survival. Control mice (n = 18) received phosphate buffered saline (PBS) vehicle only. The severity of EAE clinical disability in the hGP-transplanted group was significantly suppressed (P < 0.05) with concomitant inhibition of ConA and MOG-specific T cell proliferation in the spleen. Astrogliosis was reduced and a lower activity of macrophages and/or microglia was observed in the spinal cord (P < 0.05). On MRI, SPIO signal was detected within the lateral ventricle from 1 day post-transplantation and remained there for up to 34 days. BLI indicated that most cells did not survive beyond 5-10 days, consistent with the lack of detectable migration into the brain parenchyma and the histological presence of an abundance of apoptotic cells. Transplanted hGPs could not be detected in the spleen. We conclude that ICV transplantation of short-lived hGPs can have a remote therapeutic effect through immunomodulation from within the ventricle, without cells directly participating in remyelination.     

Anti-GBM nephritis in the mouse: severe proteinuria in the heterologous phase

Summary Highly reproducible anti glomerular basement membrane (GBM) nephritis has been induced in the mouse after a single injection of rabbit or goat antibody against purified homologous GBM. The severity of albuminuria was closely related to the amount of antibody given. With doses of 4 mg or more, low serum albumin concentrations, sometimes accompanied by ascites and oedema, were observed after 1 week. Glomerular injury was characterized by an initial accumulation of polymorphonuclear granulocytes followed by thrombosis and necrosis, the extent of which defined the outcome of the glomerulonephritis. With high doses of antibody the exudative lesions entered a chronic phase, while at doses lower than 2 mg remission of the lesions occurred. Immunofluorescence studies showed prompt linear fixation of the injected anti-bodies to the glomerular capillary wall, accompanied by immediate binding of C3 in a fine granular pattern. Fibrin deposits appeared at 2 h in some glomeruli, increased thereafter, and were present after one day in more than 90% of the glomeruli in mice that had received 4 mg of antibody. This new reproducible model in the mouse is suited for the study of the relationship between activation of mediator systems, histological lesions, and proteinuria.     

Humanitarianism in surgery

Purpose

Humanitarianism is by definition a moral of kindness, benevolence and sympathy extended to all human beings. In our view as surgeons working in underserved countries, humanitarianism means performing the best operation in the best possible circumstances with high income country (HIC) results and training in-country surgeons to do the same. Hernia Repair for the Underserved (HRFU), a not for profit organization, is developing a long term public health initiative for hernia surgery in Western Hemisphere countries. We report the progress of HRFUs methods to render humanitarian care.

Methods

In a collaborative effort, Creighton University and the Institute for Latin American Concern developed an outpatient surgery site for hernia surgery in Santiago, Dominican Republic. Based on this experience, we developed a sustainable care model by recruiting American and European Hernia Society expert surgeons, staff members they recommended, building relationships with local and industry partners, and selecting local surgeons to be trained in mesh hernioplasty. HRFU then extended the care model to other Western Hemisphere countries.

Results

Between 2004 and 2015, the HRFU elective hernia morbidity and mortality rates for 2052 hernia operations were 0.7 and 0%, respectively. This is consistent with outcomes from HICs and confirms the feasibility of a public health initiative based on the principles of the Preferential Option for the Poor.

Conclusions

HRFU has recorded HIC morbidity and mortality rates for hernia surgery in low and middle income countries and has initiated a new surgical training model for sustainability of effect.

     

Psychiatric disorders,acne and systemic retinoids: comparison of risks

Background: The link between isotretinoin, treatment of a severe form of acne, and psychiatric disorders remains controversial, as acne itself could explain the occurrence of psychiatric disorders. This study aims at assessing the disproportionality of psychiatric adverse events reported with isotretinoin in the French National PharmacoVigilance Database, compared with other systemic acne treatments and systemic retinoids.

Materials and methods: Data were extracted from the French National PharmacoVigilance Database for systemic acne treatments, systemic retinoids and drugs used as comparators. Each report was subjected to double-blind analysis by two psychiatric experts. A disproportionality analysis was performed, calculating the number of psychiatric ADRs divided by the total number of notifications for each drug of interest.

Results: Concerning acne systemic treatments: all 71 reports of severe psychiatric disorders involved isotretinoin, the highest proportion of mild/moderate psychiatric adverse events was reported with isotretinoin (14.1%). Among systemic retinoids, the highest proportion of severe and mild/moderate psychiatric events occurred with isotretinoin and alitretinoin.

Conclusion: Our study raises the hypothesis that psychiatric disorders associated with isotretinoin are related to a class effect of retinoids, as a signal emerges for alitretinoin. Complementary studies are necessary to estimate the risk and further determine at-risk populations.     

Central inferior bisegmentectomy (S4B+S5) for gallbladder carcinoma treatment: a series of seven resectable cases

BACKGROUND: Despite its rarity, gallbladder cancer is an aggressive type of neoplasia with a very poor prognosis. The best resection for oncological purposes continues to be right hepatectomy extended to segment IV. However, bisegmentectomy IV-V is becoming an interesting alternative because of greater preservation of the parenchyma. AIM: To report the early and late results from bisegmentectomy IV-V in cases of carcinoma of the gallbladder. METHODS: A series of seven cases of invasive carcinoma is presented (six women and one man). These patients underwent bisegmentectomy IV-V at the General Surgery Service of the Teaching Hospital of the ABC Medical School, Santo André, SP, Brazil. The study was conducted between 2002 and 2006. The patients ages ranged from 52 to 72 years. The diagnosis was preoperative (radiological) in five cases, which were all confirmed by intraoperative frozen-tissue examination, while in two cases the diagnosis was postoperative, following open cholecystectomy. RESULTS: The duration of the operation ranged from 180 to 340 minutes. The quantity of intraoperative bleeding ranged from 200 to 1500 mL. There were two major complications but no mortality. Six patients did not present any recurrence over the course of 3 to 30 months of follow-up. CONCLUSION: Bisegmentectomy IV-V may constitute a curative surgical alternative for treating gallbladder cancer. This procedure presents acceptable morbidity and mortality.     

Posterior C1-C2 transarticular screw fixation in the treatment of displaced type II odontoid fractures in the geriatric population—review of seven cases

BACKGROUND

Seven geriatric patients presented with displaced Type II odontoid fractures. All patients underwent a posterior C1-C2 transarticular fixation between November 1994 and December 1996. Ages ranged between 63 and 88 years.

METHODS

Fractures were treated with placement of bilateral transarticular screws, allowing immediate fixation, except in one patient, for whom only a unilateral screw was used. An autograft interspinous strut was also placed, allowing three-point fixation. Mean follow-up was 10.6 months.

RESULTS

Six patients received rigid fixation and developed a stable union. One patient died before any follow-up could be obtained. Two other patients died within 1 year of unrelated causes. The remaining four patients remain active and independent. One intraoperative vertebral artery injury was identified. No clinical sequalae were noted.

CONCLUSION

Posterior transarticular screw fixation is a reasonable option in treating these controversial fractures. Seven geriatric patients tolerated this surgery well, and were mobilized early, avoiding complications related to external immobilization.     

Current thinking on chronic renal allograft rejection: issues, concerns, and recommendations from a 1997 roundtable discussion

Chronic rejection accounts for most renal allograft losses after the first year posttransplantation. On March 24 and 25, 1997, a roundtable of five transplant surgeons, two nephrologists, and one pathologist assembled in Dallas, Texas, to review critical issues surrounding chronic renal allograft rejection. This article summarizes the presentations and relevant discussions of this meeting regarding the cause of chronic rejection, clinical diagnoses, risk factors, future prospects for intervention strategies, and general recommendations for the transplant community. Growing evidence indicates that chronic rejection is the aggregate sum of irreversible immunologic and nonimmunologic injuries to the renal graft over time. A history of acute rejection episodes and inadequate immunosuppression, likely attributable to inconsistent cyclosporine exposure or poor patient compliance, are among the most recognizable immunologic risk factors for chronic rejection. Donor organ quality, delayed graft function, and other donor and recipient variables leading to reduced nephron mass are nonimmunologic factors that contribute to the progressive deterioration of renal graft function. Clinical management of renal transplant recipients should incorporate both immunologic- and nonimmunologic-based intervention strategies aimed at minimizing risk factors to thwart the progression of chronic rejection and improve long-term allograft and patient survival.     

Cutaneous manifestations of HIV—a detailed study of morphological variants,markers of advanced disease,and the changing spectrum

Background

Cutaneous manifestations are early and easily identifiable markers of human immunodeficiency virus (HIV) infection. They can help in predicting severity and progress of the disease and can be correlated well with CD4 counts. This study was undertaken to study the cutaneous manifestations of HIV infection and to correlate them with CD4 counts. It also aimed to study the changing spectrum of these manifestations and describe cutaneous manifestations seen in advanced disease.

Method

A total of 234 HIV-positive patients not on anti-retroviral therapy, who attended the outpatient department or were admitted as inpatients at Military Hospital, Shillong during the period between May 2008 and October 2009 were included. Cutaneous, mucosal, and genitourinary manifestations in these patients were studied in detail and were correlated with CD4 counts.

Results

Infections were the most common group of mucocutaneous manifestations, while onychomycosis was the commonly observed individual manifestation. A different set of cutaneous markers for advanced HIV disease was observed and new parameters for therapy were also arrived at.

Conclusion

Specific morphological variants of cutaneous markers may provide a better clue to early diagnosis of HIV and can help in diagnosing advanced stages of the disease. Fresh cutaneous markers are required for indicating cut-off levels of CD4 count at 350/μL for starting therapy.