Response to Replacement Iron Therapy in Sideropenic Individuals with Recrudescent Herpes Labialis

 This study investigated the effects of iron replacement on the incidence of recurrent herpes labialis and serum ferritin levels in patients with sideropenia. Ten patients with diagnosed sideropenia and a history of recrudescent herpes labialis were prescribed ferrous sulphate for a period of 3 months. Patients were questioned on the number of episodes of recrudescent herpes labialis that developed per month before treatment and the number of episodes of recrudescent herpes labialis that developed per month after the commencement of replacement iron therapy and during the follow-up period. All blood samples were collected by venipuncture for assay of ferritin levels. Serum ferritin levels were significantly increased compared to pretreatment levels (P<0.05). The number of monthly episodes of recrudescent herpes labialis was reduced from 0.78 to 0.2 episodes per month following treatment (P<0.05). The findings of this study suggest that iron replacement therapy should be further studied as a treatment option in sideropenic individuals with frequent recurrences of recrudescent herpes labialis.     

Tamoxifen Attenuates Lipopolysaccharide/Galactosamine-induced Acute Liver Failure by Antagonizing Hepatic Inflammation and Apoptosis

Bacterial lipopolysaccharide (LPS)-induced acute liver failure (ALF) is a common severe clinical syndrome in intensive care unit. No other methods are available for its prevention apart from supportive treatment and liver transplantation. Tamoxifen (TAM) was reported to attenuate ALF induced by excessive acetaminophen, while its effect on LPS-induced ALF remained unknown. For this, in the present study, we comprehensively assessed whether TAM can attenuate ALF induced by LPS/galactosamine (GaIN). Mice were given TAM once a day for three times. Twelve hours after the last treatment, mice were given LPS/GaIN (intraperitoneally [i.p.]). Survival, plasma transaminases, and histopathology were examined. Serum TNF-α and IL-1β were analyzed by ELISA. Hepatic apoptosis was analyzed by TUNEL and caspase-3 Western blotting, respectively. Compared to the model group, ALF induced by LPS/GaIN was alleviated remarkably following TAM administration, as evidenced by the improvement of survival (87.5% vs. 37.5%), hepatic swell, moderate transaminases, slightly increased serum TNF-α, IL-1β (P < 0.05), and moderate histopathology. In respect of apoptosis, severe hepatocellular apoptosis was reduced notably by TAM treatment confirmed by less TUNEL-positive hepatocytes and decreased caspase-3 cleavage. The results demonstrated that TAM could attenuate LPS/GaIN-induced ALF effectively, probably due to hepatic inflammation and apoptosis antagonism. Furthermore, it was the first report about the effect of TAM on LPS/GaIN-induced ALF.     

The effects of alendronate and calcitonin on cytokines in postmenopausal osteoporosis: a 6-month randomized and controlled study

The present study was designed to determine if levels of serum cytokines, such as interleukin (IL)-1beta, IL-2, IL-2r, IL-6, IL-6r, IL-8, IL-10, and TNF-alpha are different in osteoporotic and non-osteoporotic postmenopausal women, and to evaluate the effects of calcitonin and alendronate therapies over a six month period on serum cytokine levels in postmenopausal osteoporotic women. Serum levels of IL-2, TNF-alpha and IL-8 were found to be significantly higher (p < 0.05), and serum IL-10, and IL-6r significantly lower in the calcitonin (N=60) and the alendronate (N=60) treatment groups than in the control group (N=50) (p < 0.05). But, no significant difference was apparent between the calcitonin and alendronate treated groups before treatment. Statistically significant changes occurred in patients, with respect to the levels of serum IL-6r, and IL-8 after one month (p < 0.05), in IL-2r, IL-6r, IL-8, IL-10 after three months, and in IL-1beta, IL-6r, IL-8, IL-10 and TNF-alpha after six months of calcitonin therapy (p < 0.05). No significant difference was observed in IL-6r after one month, in IL-8 and IL-10 after three months, and in TNF-alpha after six months in the calcitonin treated group and in the control group, whereas these parameters were significantly different at baseline. In the alendronate treated group, statistically significant changes occurred in the levels of serum IL-1alpha and IL-6 after three months, and in IL-1beta, IL-6, IL-6r and TNF-alpha after six months (p < 0.05). No significant difference was observed in IL-6r after one month, in IL-10 after three months or in TNF-alpha after six months between the alendronate treatment group and the control group, whereas these parameters were significantly different at baseline. In conclusion, we suggest that; 1) not only IL-1, IL-6, TNF-alpha and IL-11 but also IL-2, IL-8 and IL-10 may have roles in the etiopathogenesis of osteoporosis, 2) calcitonin therapy have a more distinct influence on serum levels of some cytokines and have an earlier effect than alendronate therapy (especially upon IL-2r, IL-8, and IL-10). Nevertheless, further longitudinal studies are needed to identify the cytokines involved in the pathogenesis of postmenopausal osteoporosis and to evaluate the influence of different treatments on these cytokines.     

Anti-Hyperglycemic and Anti-Hyperlipidemic Potential of a Polyherbal Preparation “Diabegon” in Metabolic Syndrome Subject with Type 2 Diabetes

Background

In the present study, “Diabegon” a poly-herbal preparation, with hypoglycemic activity, was evaluated for its preventive effect in metabolic syndrome subjects with type 2 diabetes and also to reveal its side effects, on liver and kidney.

Materials and Methods

Type 2 diabetic subjects with metabolic syndrome (N=58) were categorized on the basis of age and fasting blood glucose. The grouping was as follows: Group I (35–50 yrs), Group II (51–65 yrs), Group III >65 yrs, Group IV FBS<145.9, Group V FBS>145. Each group was administered 4 gm of diabegon daily. Blood glucose levels, lipid profile, liver and kidney function of the subjects were regularly monitored within 3 months of interval to 18 months.

Results

The reduction in fasting blood glucose level ranged from 12.3% (P<0.05) to 42% (P<0.001) after 18 month of therapy whereas in postprandial blood glucose, the decrease ranged from 28% (P<0.05) to 32% (P<0.05) after 18 month of therapy. Overall reductions in the individual parameters of the metabolic syndrome subjects were significantly higher in Group I. Cholesterol level decreased from 11% to 27.2% (P<0.001), triglyceride levels decreased from 24% to 55%, VLDL and LDL levels reduced by 60% & 54% respectively after 18 months of therapy. The HDL-C level increased in all groups. Moreover, diabegon administration for 1.5 years exhibited no alteration in liver and kidney function tests, which indicate its non-toxicity.

Conclusion

Our study suggests that diabegon could be included as a preventive treatment in metabolic syndrome subjects with type 2 diabetes especially for long term treatment as it efficiently shows anti-hyperglycemic and anti-lipidemic effects with no adverse impacts on the liver and kidney.     

Tamoxifen Prevents D-galactosamine/Lipopolysaccharide-Induced Murine Acute Hepatic Failure through Inhibition of Oxidative Stress and Mmd-2 Upregulation

Oxidative stress is considered one of the major mechanisms underlying lipopolysaccharide (LPS)-induced acute liver failure (ALF). Tamoxifen has been reported to ameliorate LPS-induced ALF via the induction of monocyte to macrophage differentiation-associated 2 (Mmd-2). Whether antioxidant effects are involved remains unknown. Mice were given tamoxifen (TAM) once a day for 3 days. Twelve hours later, d-galactosamine (GaIN) and LPS were injected intraperitoneally to induce ALF. N-Acetylcysteine (NAC) was administered immediately after ALF induction as a positive control. The results showed that serum transaminases increased and hepatic antioxidants decreased significantly in the model group. ALF was alleviated markedly by TAM or NAC treatment. This demonstrated that ALF may be associated with excessive oxidative stress caused by decreased expression of antioxidant enzymes. Both TAM and NAC increased the levels and activity of these antioxidant enzymes significantly (p < 0.05). Hepatic Mmd-2 expression was downregulated in the control group while remaining stable or exhibiting elevated levels in the TAM or NAC groups. The results indicate that TAM may protect mice from GaIN/LPS-induced ALF through increased activity of antioxidant enzymes and upregulation of Mmd-2 expression.     

Amantadine therapy in renal transplant patients with hepatitis C virus infection.

BACKGROUND: To date, there is no safe and efficient treatment of hepatitis C virus (HCV) infection after renal transplantation. Recently, there were encouraging reports after using amantadine in HCV-positive immunocompetent patients. OBJECTIVES: In an open pilot study, we evaluated the efficacy and the safety of amantadine monotherapy in 8 HCV positive renal-transplant patients with chronic active hepatitis and increased alanine aminotransferase (ALT) levels. RESULTS: After 6 months of amantadine therapy (200 mg per day), there were no decrease in HCV viremia (5.87 +/- 0.37 log copies/ml at M6 versus 5.71 +/- 0.5 log copies/ml at baseline; P > 0.05). However, we found a significant decrease in ALT activity (71 +/- 17 IU/l at M6 versus 100 +/- 9 IU/l at baseline; P = 0.04), whereas the decrease in aspartate aminotransferase activity did not reach statistical significance. There were no significant changes in liver histology. The clinical and biological tolerance was very good. Finally, there were a significant decrease in cyclosporine A whole blood trough levels during therapy. CONCLUSIONS: Our study is the first one to demonstrate that amantadine monotherapy lack of efficacy in HCV renal-transplant patients. It is able to improve liver enzymes but it has no impact neither upon HCV viremia nor upon liver histology.     

The influence of high dose intravenous immunoglobulins on immunological and metabolic pattern in newly diagnosed type I diabetic patients

In autoimmune disease the functional deficiency of T suppressor cells, also described in Type I diabetes, may be restored through immunoglobulin (Ig) infusion, which increases antigen phagocytosis, NK activity, cell clones and antibody anti-idiotype responses. Sixteen Type I diabetic patients were studied: eight were treated soon after the initial correction of disease-onset glycemic deterioration with intensive intravenous (i.v.) 7S Ig treatment (0.4 g/kg/BW) for 1 week and once per week for 6 months, whilst the remaining patients constituted the control group. All patients were evaluated during the study for metabolic and immunological parameters. A reduction in insulin requirement compared to conventionally treated patients was observed at the third (0.17 +/- 0.06 vs 0.44 +/- 0.08 IU/kg/BW; P less than 0.02) and at the sixth month of therapy (0.19 +/- 0.07 vs 0.54 +/- 0.07 IU/kg/BW; P less than 0.005). Two patients ceased to require insulin therapy within the BW; P less than 0.005). Two patients ceased to require insulin therapy within the first month, showing a prolonged restoration of B-cell function. Serum C-peptide values were also significantly higher in the Ig-treated group compared to the control group after 3 and 6 months. As regards immunological parameters, patients showed a decrease in insulin antibody levels and a reduction in TAC+ cells. Intravenous Ig therapy seems able to affect positively the first phases of metabolic and immunological deterioration of Type I diabetes.     

The personality and symptoms scales of the Millon Clinical Multiaxial Inventory: sensitivity to posttreatment outcomes

This study examined patterns of consistency and change on the basic personality and symptom scales of the Millon Clinical Multiaxial Inventory (MCMI) in a sample of VA inpatient alcoholics (N = 96), who were administered the MCMI at intake and at 1 month into treatment, and in a sample of drug abusers (N = 33), who received MCMI administrations at intake into treatment and after 1 and 3 months of treatment. Both alcohol and drug abuser samples in this study showed significant changes on most personality and symptom scales between intake and 1 month into treatment. The drug abusers showed small, but significant changes on three personality scales between 1 and 3 months of treatment. No such changes on symptom scales were apparent in this analysis.     

Age-associated changes in antioxidants and antioxidative enzymes in rats

The antioxidative defence capacity was assessed in tissues from different groups of rats at 3, 12 and 24 months of age. It was observed that the levels of antioxidants, vitamin E and ascorbic acid decreased in serum without any changes in liver; whereas reduced glutathione showed lower levels in both serum and liver with advancing age. Antioxidative enzymes such as superoxide dismutase and catalase activities did not indicate appreciable changes in hepatic mitochondria, but were observed to point out divergent trends in post-mitochondrial supernatants, superoxide dismutase showed reduced activities and catalase activities enhanced with age.     

姜黄素和γ-干扰素对肝纤维化大鼠肝组织病理变化及TIMP-1表达的作用

目的:观察肝纤维化大鼠肝组织病理学变化及金属蛋白酶组织抑制因子-1(TIMP-1)的表达水平,探讨姜黄素和γ-干扰素及两者联合治疗抗肝纤维化的作用。方法:将40只雄性SD大鼠随机分为正常对照组、模型组和治疗组,治疗组中又分为姜黄素治疗、γ-干扰素治疗及联合治疗3个亚组,采用CCl4腹腔注射制作大鼠肝纤维化模型。各治疗组采取相应药物和剂量平行治疗4周,第10周末将各组大鼠处死,取肝组织切片HE染色观察组织病理学变化(包括肝纤维化程度);用半定量RT-PCR方法检测各组肝组织TIMP-1mRNA相对表达量。结果:肝组织病理学观察显示,模型组大鼠肝索排列紊乱,肝细胞变性坏死,汇管区和小叶内出现局限性纤维化,部分区域出现纤维纵隔,甚至假小叶形成,纤维化分级为Ⅳ～Ⅴ级(Ⅴ级为主),TIMP-1mRNA相对表达量较正常对照组明显升高(P<0.01);各治疗组肝组织病理变化明显改善,肝细胞变性坏死减少,肝纤维化程度明显减轻(以Ⅲ级为主),TIMP-1mRNA表达量明显低于模型组(P<0.01)。结论:姜黄素和γ-干扰素及两者联合治疗均能减轻肝纤维化大鼠组织病理学变化并下调肝组织TIMP-1mRNA表达,改善和逆转肝纤维化进程。     

Total serum IgE levels in chronic hepatitis C: influence of interferon alpha therapy.

BACKGROUND: Liver disease has been considered a prominent cause of IgE elevation. No data on serum IgE levels in chronic hepatitis C have been reported. Interferon-alpha is a standard therapy for chronic hepatitis C. Cytokine use is a promising type of immunomodulation in the treatment of IgE-mediated diseases. The effects of interferon-alpha therapy on serum IgE have not been fully evaluated. The aim of the study was to evaluate both serum IgE levels in patients with chronic hepatitis C and the course of these levels after interferon-alpha therapy. PATIENTS AND METHODS: Serum IgE was determined in 100 adult patients with chronic hepatitis C (24 atopics according to positive skin prick tests and 76 nonatopics) and in 75 healthy controls (25 atopics and 50 nonatopics). Serum IgE measurements were repeated at 1 and 3 months of therapy with recombinant interferon-alpha (3 x 106 units s.c. 3 times weekly) in 34 of these patients. RESULTS: Serum IgE levels were similar in chronic hepatitis C patients and in controls when adjusted for atopic status. Among patients with chronic hepatitis C, serum IgE levels were unrelated to liver necroinflammatory activity. A modest but statistically significant increase of IgE values was observed after interferon-alpha therapy, particularly in patients with no virological response. CONCLUSIONS: Chronic hepatitis C is not a significant cause of increased total serum IgE values. Serum IgE increase in some patients with liver disease may be related to the cause of liver injury and not to liver disease per se. Interferon-alpha therapy in patients with chronic hepatitis C is followed by no modification or even a moderate increase of serum IgE values.     

A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas

A pH-sensitive dual-targeting drug carrier (G4-DOX-PEG-Tf-TAM) was synthesized with transferrin (Tf) conjugated on the exterior and Tamoxifen (TAM) in the interior of the fourth generation PAMAM dendrimers for enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. It was found that, on average, 7 doxorubicine (DOX) molecules, over 30 PEG(1000) and PEG(2000) chains and one Tf group were bonded on the periphery of each G4 PAMAM dendrimer, while 29 TAM molecules were encapsulated into the interior of per dendrimer. The pH-triggered DOX release was 32% at pH 4.5 and 6% at pH 7.4, indicating a comparatively fast drug release at weak acidic condition and stable state of the carrier at physiological environment. The in vitro assay of the drug transport across the BBB model showed that G4-DOX-PEG-Tf-TAM exhibited higher BBB transportation ability with the transporting ratio of 6.06% in 3 h. The carrier was internalized into C6 glioma cells upon crossing the BBB model by the coactions of TfR-mediated endocytosis and the inhibition effect of TAM to the drug efflux transports. Moreover, it also displayed the in vitro accumulation of DOX in the avascular C6 glioma spheroids made the tumor volume effectively reduced.     

Hepatotoxicity of antiretroviral therapy

Hepatotoxicity is a serious complication in patients taking HAART. Coinfection with hepatitis viruses increases the risk of liver toxicity while taking antiretroviral therapy. Baseline transaminases should be checked before beginning antiretorviral therapy and all patients should be screened for pre-existing liver disease, most notably hepatitis B and C infections. Regular monitoring of transaminases is mandatory when commencing antiretroviral therapy. In patients with normal liver function, transaminases may be checked monthly after commencing HAART for the first 3 months. If stable this can be broadened to 3 month intervals. In patients with pre-existing liver disease monitoring should be performed more frequently (every 2 weeks) when initiating therapy. Once stable liver enzymes should be checked monthly. The less hepatotoxic drugs such as lamivudine and abacavir should be preferred in patients at high risk for hepatotoxicity. Risks include co-infection with hepatitis B and C viruses, a previous record of hepatotoxicity, cirrhosis, obesity and female gender. Minor enzyme elevations (< 5-fold upper normal limit) are generally safe to tolerate and usually resolve. Patients must be closely observed with regular liver function tests and a hypersensitivity type drug reaction should be excluded. The onset of clinical symptoms, elevated serum lactate or evidence of severe hepatic dysfunction (coagulopathy or elevation of ammonia levels) are suggestive of severe toxicity and HAART should be withheld. Treatment of suspected HAART related hepatotoxicity should first involve withdrawal of therapy. Hypersensitivity reactions may be treated with corticosteroids. Nucleoside-induced mitochondrial damage may improve with riboflavin or thiamine therapy.     

Serum gamma-glutamyltransferase and alkaline phosphatase in rheumatoid arthritis.

Serum gamma-glutamyltransferase (GGT) and alkaline phosphatase (AP) were assayed in 98 consecutive patients with rheumatoid arthritis. Twenty-three patients had increased GGT activities and 45 an increased AP activity. Twelve patients showed an increase in both enzyme activities and AP isoenzyme studies were performed on seven of this group. In three subjects an increase in the bone isoenzyme was observed and in three others the increase in activity was attributed to the liver isoenzyme. The remaining patient, who probably suffered from coexistent primary biliary cirrhosis, showed an increase in both bone and liver isoenzymes. The liver involvement, suggested by the alkaline phosphatase isoenzyme results, was largely confirmed by the butanol extraction of GGT. The changes in these enzymes in this small series could not be related definitely to drug therapy. It is concluded that though increases in GGT and AP are common in rheumatoid arthritis, this does not necessarily indicate hepatic involvement. Further isoenzyme studies are needed to define the extent to which organs other than the liver bring about increases in these serum enzymes in rheumatoid disease.     

Early and long-term changes of equine skeletal muscle in response to endurance training and detraining

Twenty-four 4-year-old Andalusian (Spanish breed) stallions were used to examine the plasticity of myosin heavy chain (MHC) phenotype and the metabolic profile in horse skeletal muscle with long-term endurance-exercise training and detraining. Sixteen horses underwent a training programme based on aerobic exercises for 8 months. Afterwards, they were kept in paddocks for 3 months. The remaining eight horses were used as controls. Three gluteus medius muscle biopsy samples were removed at depths of 20, 40 and 60 mm from each horse before (month 0), during (month 3) and after (month 8) training, and again after 3 months of detraining (month 11). MHC composition was analysed by electrophoresis and immunohistochemistry with anti-MHC monoclonal antibodies. Fibre areas, oxidative capacity and capillaries were studied histochemically. The activities of key muscle enzymes of aerobic (citrate synthase and 3-hydroxy-acyl-CoA-dehydrogenase) and anaerobic (phosphofructokinase and lactic dehydrogenase) metabolism and the intramuscular glycogen and triglyceride contents were also biochemically analysed. Early changes with training (3 months) included hypertrophy of type IIA fibres, a reduction of MHC-IIX with a concomitant increase of MHC-IIA, a rise in the number of high-oxidative fibres and in the activities of aerobic muscle enzymes and glycogen content. Long-term changes with training (8 months) were a further decline in the expression of MHC-IIX, an increase of slow MHC-I, additional increases of high-oxidative fibres, capillary density, activities of aerobic enzymes and endogenous glycogen; intramuscular lipid deposits also increased after 8 months of training whereas the activities of anaerobic enzymes declined. Most of exercise-induced alterations reverted after 3 months of detraining. These results indicate that endurance-exercise training induces a reversible transition of MHC composition in equine muscle in the order IIX-->IIA-->I, which is coordinated with changes in the metabolic properties of the muscle. Furthermore, a dose-response relationship was evident between the duration (in total) of training and the magnitude of muscle adaptations.     

Induction of circulating activated suppressor-like T cells by methimazole therapy for Graves' disease

Thyrostatic drug treatment of Graves' disease suppresses excessive thyroid hormone synthesis and causes a parallel decrease in serum thyroid autoantibody levels. The mechanism of this immunosuppression is unknown. We studied methimazole-induced immunoregulatory effects prospectively in 14 patients with Graves' disease treated for up to six months. The numbers of circulating activated, HLA-DR-positive T helper/inducer cells decreased gradually, from 8.3+1.7 percent (+SD) to 1.0+1.7 percent (P less than 0.001). HLA-DR-positive T suppressor/cytotoxic cells increased transiently at one month, from 2.0+1.9 percent to 12.6+6.4 percent (P less than 0.001), and returned to 2.9+3.7 percent at six months. Methimazole did not alter the HLA-DR expression of T cells in vitro. In two patients, the helper activity of T cells in inducing autoantibody secretion in vitro was substantially reduced after one month of methimazole treatment. Before treatment, large proportions of thyroid-infiltrating T-cell subsets expressed the activation markers HLA-DR, interferon-gamma, and interleukin-2 receptors, which were partially lost during therapy. Methimazole treatment was accompanied by a gradual reduction in circulating levels of thyrotropin-receptor, microsomal, and thyroglobulin autoantibodies. These results are compatible with the view that methimazole-induced immunoregulation in Graves' disease is mediated by a direct inhibitory effect on thyrocytes. This inhibition is in turn accompanied by marked changes in the proportions of activated T helper-like and T suppressor-like cells. This altered T-cell activation profile reflects, at least in part, the functional suppression of autoantibody production observed in methimazole-treated patients with Graves' disease.     

Increased growth after long-term oral 1alpha,25-vitamin D3 in childhood renal osteodystrophy.

We evaluated oral 1,25-vitamin D3 for as long as 26 months in six prepubescent children with renal osteodystrophy previously treated with vitamin D2. Therapy was given at 14 to 41 ng per kilogram per day to correct hypocalcemia and reverse bone disease. Serum levels of 1,25-vitamin D3 were initially reduced at 15 +/- 5 pg per milliliter (mean +/- S.E.M.) and after treatment rose to 54 +/- 13. Serum calcium rose from 7.5 +/- 1.6 mg per deciliter (mean +/- S.D.) to 9.8 +/- 0.6 after one month (P less than 0.02). Alkaline phosphatase activity fell from 536 +/- 298 to 208 +/- 91 IU per liter after 12 months (P less than 0.05). Serum immunoreactive parathyroid levels fell from 900 +/- 562 microliter eq per milliliter 411 +/- 377. Healing of rickets and subperiosteal erosions was found. Remineralization of bone was demonstrated by the photon absorption technic. In four patients growth velocity, evaluated for 12 months before and after therapy, increased from 2.6 +/- 0.8 to 8.0 +/- 3.2 cm per year. Growth velocity per year increased from less than third percentile in each to the 10th to 97th percentile after therapy. Height increment ranged from 27 to 113 per cent of that expected for change in chronologic age and 40 to 114 per cent expected for change in bone age after therapy. This trial demonstrates that oral 1,25-vitamin D3 can reverse renal bone disease and increase growth in uremic children.