The circadian dynamics of the hippocampal transcriptome and proteome is altered in experimental temporal lobe epilepsy.

Gene and protein expressions display circadian oscillations, which can be disrupted in diseases in most body organs. Whether these oscillations occur in the healthy hippocampus and whether they are altered in epilepsy are not known. We identified more than 1200 daily oscillating transcripts in the hippocampus of control mice and 1600 in experimental epilepsy, with only one-fourth oscillating in both conditions. Comparison of gene oscillations in control and epilepsy predicted time-dependent alterations in energy metabolism, which were verified experimentally. Although aerobic glycolysis remained constant from morning to afternoon in controls, it increased in epilepsy. In contrast, oxidative phosphorylation increased in control and decreased in epilepsy. Thus, the control hippocampus shows circadian molecular remapping, which is altered in epilepsy. We suggest that the hippocampus operates in a different functioning mode in epilepsy. These alterations need to be considered when studying epilepsy mechanisms, designing drug treatments, and timing their delivery.

Influence of hepatitis G virus coinfection on the clinical course of chronic hepatitis C.

Hepatitis G virus (HGV) is a parenterally transmitted virus, frequently associated with hepatitis C virus infection. Hepatitis G virus RNA was detected by reverse transcription-polymerase chain reaction in the serum of 40 patients with chronic hepatitis C. Nine (22.5%) patients had evidence of hepatitis G virus viraemia. No significant epidemiological or virological differences could be demonstrated between subjects infected with both hepatitis G virus and hepatitis C virus and subjects infected with hepatitis C virus alone. Aminotransferase values were comparable between the two groups, whereas higher levels of cholestatic enzymes (P< 0.001) were reported in the hepatitis G virus/hepatitis C virus-positive patients. A liver biopsy was performed on all 40 patients no later than 6 months before recruitment. The mean histological activity index did not differ between hepatitis G virus-positive and hepatitis G virus-negative patients, whereas specific histological features such as macrovesicular steatosis, portal granulomas, and bile duct damage were more commonly observed among the coinfected patients. The results indicate that coinfection with hepatitis G virus probably does not have a significant effect on hepatitis C virus-induced hepatic damage.

Serum hepatitis G virus (HGV) RNA in multitransfused thalassemics from eastern Sicily.

The prevalence of hepatitis G in a multitransfused population was studied. HGV did not appear to be a major contributor to liver pathology in this group and the prevalence was surprisingly low.

Leucocyte interferon-alpha retreatment for chronic hepatitis C patients previously intolerant to other interferons.

The activity and tolerability of a retreatment cycle with leucocyte interferon-alpha (IFN-alpha) (6 million units (MU) three times weekly for 12 months) was evaluated in a group of 22 hepatitis C patients who had been intolerant to a previous course of lymphoblastoid IFN-alpha. Seven patients (31%) discontinued the new therapy owing to either a lack of response (six patients) or to severe leucopenia (one patient). Fifteen patients (68%) completed the 12-month treatment: all had a biochemical response and 10 (45%) also had disappearance of serum HCV RNA (complete response). Mild adverse reactions (fever, headaches and diarrhoea) were seen in these patients during retreatment. After 12 months of follow-up, 11 patients (50%) still maintained the biochemical response (long-term response); seven of these patients (32%) were also negative for serum HCV RNA. Biochemical and complete responses, at the end of both treatment and follow-up, were similar to those seen with lymphoblastoid IFN-alpha. The full dose of leucocyte IFN-alpha, when used in patients previously intolerant to the same dosage of lymphoblastoid IFN-alpha, was better tolerated: only one of the 15 patients who completed the 12-month treatment had a severe adverse event leading to withdrawal vs 22 of 68 patients treated with lymphoblastoid IFN-alpha. Furthermore, there were no manifestations of serological or clinical autoimmunity caused by leucocyte IFN-alpha, even in patients with autoantibodies associated with previous IFN therapy.

Serum cytokines as predictors of clinical outcome in AIDS-related intestinal cryptosporidiosis.

BACKGROUND: Clinical variability in the natural course of cryptosporidiosis in patients affected by acquired immunodeficiency syndrome has been correlated to the degree of T-cell immunosuppression; however, cryptosporidiosis can occur as a self-limiting disease even in patients with very low T-lymphocyte count. AIMS: We tested the serum values of a panel of cytokines in AIDS patients with cryptosporidial enteritis in order to evaluate their role in predicting the clinical outcome of the disease. PATIENTS AND METHODS: Thirty one HIV-positive patients with cryptosporidiosis and a CD4+ count of less than 100/mm3 were studied. Interleukin-2, Interleukin-4, Interleukin-10, Interferon-gamma, Interleukin-12, Tumor Necrosis Factor alpha values were measured in serum at diagnosis. RESULTS: Interleukin-4 and Interleukin-10 concentration was significantly lower in patients with mild disease whereas serum Interleukin-2 and -12 was higher in this same group. The serum level of Interferon-gamma did not differ in relation to the severity of the disease. Patients with self-limiting diarrhoea showed significantly lower levels of Tumor Necrosis Factor-alpha than subjects who did not show any clinical improvement. CONCLUSIONS: In our study, it has been shown that cytokine levels in serum may represent early predictive markers both for the severity of symptoms and the clinical outcome of cryptosporidial enteritis in AIDS patients with a low CD4+ count.

Acute hepatitis E in Catania (eastern Sicily) 1980-1994. The role of hepatitis E virus.

Between 1980 and 1994, 540 patients with acute viral hepatitis were admitted to hospital at the Department of Infectious Diseases of Catania (eastern Sicily). Twenty-five patients out of 540 were assessed as having non-A, non-B, non-C hepatitis. These subjects were studied for anti-HEV IgM and IgG seroprevalence by testing serial serum samples collected 1, 4, 12 and 24 weeks after the onset of acute disease. Fourteen of 25 samples (56%) seroconverted to anti-HEV IgG antibodies. No sample was positive for anti-HEV IgG at week 1, ten samples were positive at week 4 and the remainder at week 12. Anti-HEV reactivity was maintained until week 24 in all cases. In 11 of the 14 patients seroconverting to anti-HEV, the presence of IgM anti-HEV was found, which appeared in the sample from week 1 and gradually disappeared thereafter. Identified risk factors for HEV transmission included travel in the tropics and shellfish ingestion (anti-HEV positive versus anti-HEV negative: p < 0.05). HEV-related hepatitis is not yet a major public health problem in Sicily but, from our data, the trend of its incidence is clearly upwards. The high incidence of faecally-orally transmitted diseases in Sicily, the crucial position of Sicily in the middle of the Mediterranean Sea (where HEV largely circulates) and the increase of migration from developing countries are all factors which should increase awareness for a more active surveillance of the spread of HEV in our area.

Bilateral non-communicating paraurethral meatus in Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a complex multisystemic congenital disorder due to an interstitial deletion of chromosome 15q11-13 or to maternal uniparental disomy. Molecular genetic testing is complex, and often requires DNA from both parents, which is not always available. An accurate medical history and presenting clinical signs are frequently the only tools for the clinical diagnosis of this syndrome, therefore it is important to have complete and accurate criteria. The presence of a bilateral non-communicating paraurethral meatus in a 9-year-old female patient affected by PWS, previously unreported in the literature, should induce clinicians to look for this sign when examining such patients.

[Synergic effect of albendazole plus metronidazole association in the treatment of metronidazole-resistant giardiasis]. / Efficacia sinergica dell'associazione albendazolo-metronidazolo nella giardiasi refrattaria a monoterapia con metronidazolo.

Twenty patients with intestinal giardiasis, already resistant to 3-5 previous courses of oral metronidazole, were randomly distributed into 2 different groups: 10 subjects were given oral albendazole (440 mg/two times per day for 7 days) and 10 were submitted to the association of albendazole (400 mg/two times per day for 7 days) plus metronidazole (250 mg/three times per day for 7 days). All patients were evaluated both for clinical and parasitological status, immediately before and after therapy and, then, 4 weeks later. Only 3 patients of those treated with albendazole alone, showed a clinical and parasitological remission at the end of therapy, and one of them relapsed 4 weeks later. All patients who underwent albendazolemetronidazole association responded to the therapy and all except one were defined as "cured" 4 weeks later. Our study demonstrates that albendazole alone is not an effective therapeutic alternative for "metronidazole-resistant" giardiasis. The association of metronidazole plus albendazole seems synergic and deserves further studies.