Treatment of Renal Fungal Ball with Fluconazole Instillation Through a Nephrostomy Tube: Case Report and Literature Review.

BACKGROUND Urinary tract candida infection can be due either to hematogenous dissemination of the organism or a retrograde infection. In debilitated or immunosuppressed septic patients, who have upper urinary tract obstruction with renal filling defect, fungal infection should be considered. We report on a patient with sepsis and renal fungal ball who was treated with percutaneous nephrostomy and intravenous antifungal agent, but the patient did not respond so instillation of fluconazole through nephrostomy was given. CASE REPORT A 60-year-old male patient with a known case of diabetes mellitus with refractory urine retention underwent transurethral resection of the prostate. Postoperatively, the patient developed recurrent high-grade fever with left loin pain, and elevated septic parameters; urine and blood culture were positive for Candida albicans. Computed tomography urography showed left hydronephrosis with filling defect in the left renal pelvis with suspected renal fungal ball. Left percutaneous nephrostomy was performed and intravenous fluconazole started but the fever did not subside, therefore, the treatment was changed to anidulafungin. The patient improved but urine from both the bladder and the nephrostomy remained positive for candida. Instillation of fluconazole at 300 mg in 500 mL normal saline was applied through the nephrostomy tube over 12 hours at 40 mL/hour for 7 days. CONCLUSIONS Renal fungal ball is rare but can be serious, especially in immunocompromised patients. Management options for renal fungal ball include intravenous antifungal agents and percutaneous nephrostomy with antifungal instillation of antifungal agents. The objective of this case report was to document treatment success with the use of fluconazole instillation through a nephrostomy tube.

CURCUMA LONGA AS MEDICINAL HERB IN THE TREATMENT OF DIABET- IC COMPLICATIONS.

Curcuma longa L. (turmeric) of ginger family (Zingiberaceae) belongs to the group of oldest cultivated spice plants in the south-east Asian countries. For many years rhizome of this plant has been used also as a safe and active drug for the treatment of various.chronic diseases, especially of diabetes mellitus (DM). The active substance of turmeric - curcumin (diferuloylmethane), possesses multiple therapeutic properties. In recent years, many detailed research (tests in vito and in vivo) along with clinical trials have revealed its very valuable biological activities related to its anti-inflammatory, antioxidant and cancer preventive properties, which are presented in numerous publications (1-6). At the molecular level it has been stated that curcumin inhibits cell proliferation, metastasis creation and apoptosis. Currently, great attention has been focused on curcumin as a blocker of TNF-s, which are the principal mediators of most inflammation-related disturbances (7). The main cause of blocking the broadly extended pharmacological and clinical investigations of curcumin is its extremely low solubility in water and in organ fluids. This feature consequently limits its systemic bioavailability and makes use of curcumin as a therapeutic remedy (to date) difficult. The primary aim of presently conducted research is to achieve increased solubilization and bioavailability of this promising nontoxic agent.

Glycine prevents metabolic steatohepatitis in diabetic KK-Ay mice through modulation of hepatic innate immunity.

Strategies for prevention and treatment of nonalcoholic steatohepatitis remain to be established. We evaluated the effect of glycine on metabolic steatohepatitis in genetically obese, diabetic KK-Ay mice. Male KK-Ay mice were fed a diet containing 5% glycine for 4 wk, and liver pathology was evaluated. Hepatic mRNA levels for lipid-regulating molecules, cytokines/chemokines, and macrophage M1/M2 markers were determined by real-time RT-PCR. Hepatic expression of natural killer (NK) T cells was analyzed by flow cytometry. Body weight gain was significantly blunted and development of hepatic steatosis and inflammatory infiltration were remarkably prevented in mice fed the glycine-containing diet compared with controls. Indeed, hepatic induction levels of molecules related to lipogenesis were largely blunted in the glycine diet-fed mice. Elevations of hepatic mRNA levels for TNFα and chemokine (C-C motif) ligand 2 were also remarkably blunted in the glycine diet-fed mice. Furthermore, suppression of hepatic NK T cells was reversed in glycine diet-fed KK-Ay mice, and basal hepatic expression levels of NK T cell-derived cytokines, such as IL-4 and IL-13, were increased. Moreover, hepatic mRNA levels of arginase-1, a marker of macrophage M2 transformation, were significantly increased in glycine diet-fed mice. In addition, dietary glycine improved glucose tolerance and hyperinsulinemia in KK-Ay mice. These observations clearly indicate that glycine prevents maturity-onset obesity and metabolic steatohepatitis in genetically diabetic KK-Ay mice. The underlying mechanisms most likely include normalization of hepatic innate immune responses involving NK T cells and M2 transformation of Kupffer cells. It is proposed that glycine is a promising immunonutrient for prevention and treatment of metabolic syndrome-related nonalcoholic steatohepatitis.

Clinical, microbial, and immune responses observed in patients with diabetes after treatment for gingivitis: a three-month randomized clinical trial.

BACKGROUND: Although patients with diabetes are frequently affected by periodontitis, only a few investigations have focused on gingivitis in this at-risk population. This randomized placebo-controlled clinical trial compared the response to a gingivitis treatment protocol that combined mechanical procedures and daily use of an essential oil (EO) mouthrinse between patients with and without diabetes. METHODS: The whole-mouth periodontal probing depth (PD), gingival index (GI), and plaque index (PI) were monitored in gingivitis cases among systemically healthy patients (n = 60) or those with diabetes (n = 60) at baseline and 3 months after treatment. Levels of Porphyromonas gingivalis, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and total bacterial load were determined by a real-time polymerase chain reaction in intrasulci plaque samples. The volume of gingival crevicular fluid (GCF) was quantified, and interleukin-1ß (IL-1ß) levels were determined in GCF samples. After a full-mouth ultrasonic debridement, patients were randomly assigned to an EO or a placebo rinse for 90 days (40 mL/day). The data were analyzed through repeated-measures analysis of variance and multiple comparisons Tukey tests (P <0.05). RESULTS: GI was more severe in the diabetes group. Diabetes impaired GI and reduced GCF volume. PD, bacterial levels, and IL-1ß improved similarly in both systemic conditions. The adjunctive use of EO provided greater reductions of PI, GI, total bacterial load, T. forsythia, A. actinomycetemcomitans, and GCF volume. CONCLUSIONS: Response to gingivitis treatment in patients with diabetes can slightly differ from that in patients without diabetes. Daily use of an EO mouthrinse after ultrasonic debridement benefited patients with and without diabetes.

Hyperbaric oxygen treatment reduces neutrophil-endothelial adhesion in chronic wound conditions through S-nitrosation.

Hyperbaric oxygen (HBO) therapy is an effective treatment for diabetic chronic wounds. HBO reduces inflammation and accelerates wound healing, by mechanisms that remain unclear. Here we examined a mechanism by which HBO may reduce neutrophil recruitment, through changes in endothelial and neutrophil adhesion molecule expression and function. Human umbilical vein endothelial cells and neutrophils were exposed to selected chronic wound conditions, comprising hypoxia in the presence of lipopolysaccharide and tumor necrosis factor-alpha, and then treated with HBO. We observed neutrophil adhesion to endothelial cells following treatment with chronic wound conditions, which was reversed by HBO treatment. This was partly explained by reduced expression of endothelial intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by HBO. No changes in neutrophil adhesion molecule expression (CD18, CD11b, CD62L, CD31) were observed following HBO treatment. However, HBO decreased hydrogen peroxide generation by neutrophils, and induced nitrous oxide-related protein modifications. The transnitrosating agent S-nitroso-L-cysteine ethyl ester (600 µM) also reduced neutrophil adhesion to human umbilical vein endothelial cell monolayers, and the iNOS inhibitor 1400 W (10 µM) and HgCl2, which promotes the decomposition of S-nitrosothiols (1 mM), reversed the effect of HBO, suggesting that S-nitrosation may inhibit neutrophil-endothelial cell adhesion. This study indicates that HBO could reduce inflammation in wounds through reduced neutrophil recruitment, mediated by S-nitrosation.

Antioxidant and antiinflammatory activities of curcumin on diabetes mellitus and its complications.

Diabetes mellitus (DM) has reached pandemic status and shows no signs of abatement. It can severely impair people's quality of life and affects patients all over the world. Since it is a serious, chronic metabolic disease, it can bring about many kinds of complications, which can in turn increase mortality. In recent decades, more and more studies have shown that oxidative stress and inflammatory reactions play critical roles in the pathogenesis of DM. There is an increasing demand for natural antidiabetic medicines that do not have the same side effects as modern drugs. Curcumin, a phytochemical found in the spice turmeric, has been used in India for centuries, and it has no known side effects. It has been shown to have some beneficial effects against various chronic illnesses. Many of these therapeutic actions can be attributed to its potent anti-oxidant and anti-inflammatory activities. In view of the oxidative stress and inflammatory mechanisms of DM, curcumin can be considered suitable for the prevention and amelioration of diabetes. In this review, we summarize the nosogenesis of DM, giving primary focus to oxidative stress and inflammation. We discuss the anti-oxidant and anti-inflammatory activities of curcumin in DM and its ability to mitigate the effects on DM and its associated complications in detail.

Danshensu ameliorates the cognitive decline in streptozotocin-induced diabetic mice by attenuating advanced glycation end product-mediated neuroinflammation.

Spatial learning and memory are impaired in diabetic animals. The interaction of advanced glycation end products (AGEs) with the receptor of AGEs (RAGE), resulting in the activation of nuclear factor-κB (NF-κB), plays an important role in pathways leading to the cytotoxic effects to neurons. Danshensu, a compound from Salvia miltiorrhiza Bunge, has neuroprotective effects. This study aimed to investigate the role of AGE-mediated neuroinflammation in learning and memory deficits and the effect of Danshensu on the cognitive decline in diabetic mice. C57BL/6 mice were injected intraperitoneally with streptozotocin. Sodium Danshensu (sodium salt of Danshensu) was administered at a dose of 15, 30, or 60 mg/kg for 12 weeks. The results showed that diabetes caused impairment in acquisition and retrieval processes, as demonstrated by performance in the Morris water maze test. Danshensu not only reduced the mean escape latency but also increased the percentage of time spent in the target quadrant. Western blot analysis revealed that there was a significant increase in the expression of RAGE, p-p38, and COX-2, and the NF-κB activation. Danshensu partly blocked the expression of RAGE, p-p38, and COX-2, and NF-κB activation, and inhibited the increase of TNF-α, IL-6, and PGE2. However, Danshensu did not affect body weight and the levels of blood glucose, glycosylated hemoglobin, insulin, and AGEs. These findings demonstrate that AGE-mediated neuroinflammation plays an important role in learning and memory deficits in diabetic mice and that Danshensu may provide a potential alternative for the prevention of cognitive impairment associated with diabetes by attenuating AGE-mediated neuroinflammation.

Anticoagulatory, antiinflammatory, and antioxidative effects of protocatechuic acid in diabetic mice.

Content of protocatechuic acid (PA) in eight locally available fresh fruits was analyzed, and the protective effects of this compound in diabetic mice were examined. PA at 1%, 2%, and 4% was supplied to diabetic mice for 8 weeks. PA treatments significantly lowered plasma glucose and increased insulin levels. PA treatments at 2% and 4% significantly lowered plasminogen activator inhibitor-1 activity and fibrinogen level; increased plasma activity of antithrombin-III and protein C; decreased triglyceride content in plasma, heart, and liver; elevated glutathione level and the retention of glutathione peroxidase and catalase activities in heart and kidney. PA treatments at 2% and 4% also significantly lowered plasma C-reactive protein and von Willebrand factor levels and reduced interleukin-6, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 levels in heart and kidney. These results support that protocatechuic acid could attenuate diabetic complications via its triglyceride-lowering, anticoagulatory, antioxidative, and antiinflammatory effects.

Diabetes and rheumatic diseases.

PURPOSE OF REVIEW: This review summarizes recent advances in the field of diabetes and rheumatic disease. These conditions exert a significant healthcare burden on our society and much remains to be learned regarding their pathophysiology and treatment. RECENT FINDINGS: We summarize new insights into diabetes and its association with osteoarthritis, rheumatoid arthritis, carpal tunnel syndrome, osteoporosis, diffuse idiopathic skeletal hyperostosis, crystalline arthropathy, neuropathic arthropathy, and tendinopathy. Diabetes has major effects on connective tissues, which have significant impact on both the development and outcome of these diseases of cartilage, bone, ligament, and tendon. An improved understanding of the mechanisms through which diabetes alters connective tissue metabolism should lead to better preventive and therapeutic interventions. SUMMARY: Incremental progress has been made in understanding the interactions between diabetes and common musculoskeletal syndromes. Although this review highlights exciting areas of future interest, more work in this field is certainly warranted.

Increased leptin expression selectively in the hypothalamus suppresses inflammatory markers CRP and IL-6 in leptin-deficient diabetic obese mice.

Low-grade systemic inflammation, as indicated by increased circulating levels of inflammatory markers CRP and IL-6, is linked to increased risks for cardiovascular diseases (CVD) and diabetes mellitus in obese subjects. Whereas hyperleptinemia in obesity are associated with increased CRP and IL-6 release, the hypothalamic versus peripheral site of leptin action has not been ascertained. The effects of increased leptin supply selectively in the hypothalamus by gene therapy on pro-inflammatory CRP and IL-6 levels and on markers of diabetes in the circulation of ob/ob mice displaying either age-related or dietary obesity were assessed. A recombinant adeno-associated viral vector encoding either green-fluorescent protein (control) or leptin gene was injected intracerebroventricularly. Five weeks later, one-half of each of the vector groups was switched to high-fat diet consumption and the other half continued to consume regular low-fat chow diet. Body weight and visceral white adipose tissue were drastically reduced and hyperinsulinemia and hyperglycemia were abrogated by leptin gene therapy, independent of the dietary fat content. The elevated plasma CRP and IL-6 levels seen in obese ob/ob mice receiving the control vector, regardless of the fat content of the diet, were markedly suppressed by increased hypothalamic leptin in both groups. The results show for the first time that leptin deficiency elevates and reinstatement of leptin selectively in the hypothalamus suppresses the release of pro-inflammatory biomarkers, a response likely to alleviate CVD associated with obesity.

Psychoneuroimmune implications of type 2 diabetes.

The idea that type 2 diabetes is associated with augmented innate immune function characterized by increased circulating levels of acute phase reactants and altered macrophage biology is fairly well established, even though the mechanisms involved in this complex interaction still are not entirely clear. To date, the majority of studies investigating innate immune function in type 2 diabetes are limited to the context of wound healing, atherosclerosis, stroke, and other commonly identified comorbidities. Several important recurring themes come out of these data. First, type 2 diabetes is associated with a state of chronic, subclinical inflammation. Second, in macrophages, type 2 diabetic conditions enhance proinflammatory reactions and impair anti-inflammatory responses. Third, after acute activation of the innate immune system in type 2 diabetes, recovery or resolution of inflammation is impaired. The consequences of type 2 diabetes-associated inflammatory alterations on PNI processes have been recognized only recently. Given the impact of diminished emotional well-being on the quality of life in patients who have type 2 diabetes, diabetes-induced exacerbation of PNI responses should be considered a serious complication of type 2 diabetes that warrants further clinical attention.