The antioxidant activity of chondroitin-4-sulphate, in carbon tetrachloride-induced acute hepatitis in mice, involves NF-kappaB and caspase activation

Background and purpose:

Reactive oxygen species (ROC) are the main causes of carbon tetrachloride (CCl₄)-induced acute liver injury. Chondroitin-4-sulphate (C4S) is known to inhibit lipid peroxidation through antioxidant mechanisms. Activation of nuclear factor (NF)-κB and caspases may strongly intensify inflammation and cell damage, in addition to that directly exerted by ROS. We investigated whether treatment with C4S, besides exerting antioxidant activity, was able to modulate NF-κB and apoptosis activation in CCl₄-induced liver injury in mice.

Experimental approach:

Acute hepatitis was induced in mice by an i.p. injection of CCl₄. Varying doses of C4S were administered i.p. 1 h before, 6 and 12 h after CCl₄ injection. 24 h after CCl₄ injection, the mice were killed for biochemical and histological analysis.

Key results:

CCl₄ injection produced: marked elevation of alanine aminotransferase and aspartate aminotransferase; hepatic membrane lipid peroxidation, assayed by 8-isoprostane levels; and depletion of reduced glutathione and superoxide dismutase. CCl₄ also decreased NF-κB translocation and IkBα, and increased gene expression of mRNA and protein of metalloproteases (MMP)-2 and -9, and of pro- and cleaved forms of caspases-3 and -7. There was also increased liver polymorphonuclear infiltration, evaluated by elastase assay, and hepatic cell disruption.C4S treatment inhibited lipid peroxidation; blocked NF-κB activation and IkBα protein loss; decreased mRNA and proteins for MMPs and caspases; restored endogenous antioxidants; limited hepatic polymorphonuclear accumulation and tissue damage.

Conclusions and implications:

As antioxidants may inhibit NF-κB and caspase activation, we hypothesize that treatment with C4S was able to inhibit NF-κB and apoptosis activation in hepatic injury.     

Healing traditions and men's sexual health in Mumbai, India: the realities of practiced medicine in urban poor communities

Men's pre- and extra-marital sexual behavior has been identified as the primary factor in the growing HIV/STI epidemic among both males and females in India. One major barrier to reaching men has been their underutilization of public health services, which has severely limited programs geared to prevention and early case identification. A significant number of men in India have strong culturally-based sexual health concerns, much of which are derived from "semen-loss" and deficiencies in sexual performance. This paper reports on an ongoing Indo-US project that has focused on men's concerns about sexual health problems and assesses the services provided by non-allopaths in three low-income communities in Mumbai. Findings indicate that the primary health resources for these men are private, community-based non-allopaths, who identify themselves as ayurvedic, unani and homeopathic providers. The paper suggests that the combination of strong culturally-based sexual health concerns and the presence of private non-allopaths who manage these problems present a window of opportunity for intervention programs to address the challenge of HIV/STI prevention and early case identification in India.     

Epidemic dissemination ofSalmonella enterica spp.enterica serovar Bovismorbificans in southern Italy in the years 1989–1991

Epidemic strains ofSalmonella enterica subsp.enterica serovar Bovismorbificans isolated in southern Italy during the years 1989–1991 were submitted to a molecular epidemiological study in comparison with isolates identified in the years 1980–1988 in the same geographic area. Genomic DNA fragments obtained by digestion withBglI orEco RI hybridized withEscherichia coli rRNA to produce three distinct, but highly related patterns. Ribotype 1, which had never been identified before 1989, was found to characterize most of the strains identified between 1989 and 1991. Such a finding supports the hypothesis of emergence and spread of a new bacterial clone associated with the increased number of human infections reported in the same years in southern Italy.     

The use of cisplatin as radiosensitizing agent in advanced tumors of the head and neck. Randomized study]

This study was aimed at assessing whether c-DDP administration immediately before radiotherapy could increase frequency and duration of objective responses, as well as survival, in patients affected with locally advanced stages of squamous carcinomas of the head and neck. All patients had already undergone two induction cycles according to the CABO schedule. Ninety-six of 108 treated patients could be evaluated. Treatment schedule consisted in: 1) randomized distribution of patients into two groups before induction chemotherapy; 2) two cycles of induction chemotherapy according to the CABO schedule in all patients; 3) radiation therapy: the patients in group A were given 5 mg/mq of i.v. cisplatin, 30-60 minutes before each session. The results from the two groups were compared and no significant differences were observed regarding objective response (82.5% in group A vs. 86% in group B), response duration and overall survival rates. Even though toxicity was higher in the patients in group A, therapeutic protocol never needed be modified.     

5-Fluorouracil combined with the pure L-stereoisomer of leukovorin calcium to treat advanced colon-cancer patients - a phase-ii study

A theoretical superiority of 5-fluorouracil (FUra) activity when combined with l-leucovorin (LV) might be postulated on the basis of a possible interference of the inactive d-stereoisomer of LV with the active l-form. We treated 47 patients by means of FUra (370 mg/m2/day) and l-LV (100 mg/m2/day), for 5 consecutive days, every 4 weeks. An objective response was observed in 12 patients (25.5%, 95% confidence interval: 12.5-38.5%), with 2 complete responses. As regards toxicity, 53.1% of the patients experienced mucositis, 51% diarrhea, 31.9% nausea and vomiting, 12.7% leukocytopenia, 8.5% cutaneous toxicity, 4.25% neurotoxicity, conjunctivitis and phlebitis. This regimen appears to be substantially superimposible to the classic FUra/d,l-LV combination. Therefore, the use of l-LV, in those countries where this compound is commercially available, should not be discouraged.     

The hemangioma-sternum bifidum malformation syndrome. Report of a patient

We present a male patient with a facial haemangioma extending from the lower left lid to the malar region and the upper left lip. The patient also presents a 1 cm round cutaneous notch on the upper third of the sternum. There are not other physical anomalies. The characteristics of the clinical picture suggest the diagnosis of sternal cleft-haemangiomas malformative spectrum (OMIM 140850).