Vascular endothelial growth factor and angiogenin levels during fetal development and in maternal diabetes

We evaluated the concentrations of vascular endothelial growth factor (VEGF) and angiogenin in the umbilical cord blood from 14 fetuses with erythroblastosis or alloimmune thrombocytopenia and at birth from 28 preterm fetuses, from 42 healthy term fetuses, and from 24 term fetuses born to mothers with insulin-treated diabetes. A correlation appeared between VEGF and angiogenin levels (r = 0.44, p = 0.038). The gestational age correlated with both VEGF (r = 0.38, p = 0.0008) and angiogenin levels (r = 0.80, p = 0.0001). The concentration of VEGF was lower in fetuses born to mothers with insulin-treated diabetes than in the healthy term fetuses (p = 0.0028), but this difference was absent for angiogenin (p > 0.05). In conclusion, in umbilical cord plasma, a developmental increase was evident in concentrations of VEGF and angiogenin during the last trimester of gestation. That the umbilical cord VEGF level was lower in term fetuses born to mothers with diabetes than in term fetuses of healthy mothers may be associated with an aberrant fetal vascular development in diabetic pregnancies.     

Regioselective induction of liver glutathione transferase by ethanol and acetone

Both ethanol and acetone are substrates and inducers of the cytochrome P450 IIEI. This isoenzyme is induced in the perivenous region, which may explain the centrilobular damage elicited by several hepatotoxins being substrates for P450 IIE1. Here we demonstrate that induction of glutathione S-transferase after ethanol and acetone treatment is also restricted to the perivenous region, suggesting regiospecific enhancement of the transferase associated cellular defence capacity. The total glutathione peroxidase activity does not increase after the induction.     

Interstitial pneumonitis and coinfection of human herpesvirus 6 and Pneumocystis carinii in a patient with hypogammaglobulinemia

Human herpesvirus 6 (HHV-6) has occasionally been associated with cases of interstitial pneumonitis, mainly in individuals with impaired cellular immunity. Here we report for the first time severe interstitial pneumonitis with simultaneous HHV-6 and Pneumocystis carinii infections in the lung tissue of a young patient with hypogammaglobulinemia.     

HHV-6B is frequently found in the gastrointestinal tract in kidney transplantation patients

In immunosuppressed patients human herpesvirus 6 (HHV-6) reactivations are common. The aim of the study was to determine to which extent HHV-6 can be found in the gastrointestinal tract in kidney transplant recipients and in patients on chronic dialysis. The HHV-6 and cytomegalovirus (CMV) examinations were performed on gastro duodenal and colon biopsy specimens obtained from 81 kidney transplant recipients and on 46 chronic dialysis patients. The HHV-6 and CMV were demonstrated by immunohistochemistry detecting both HHV-6A and HHV-6B, and CMV-specific antigens. The HHV-6B-positive cells, were found in gastroduodenal biopsy specimens from 34% of the transplant recipients and 28% of the patients on chronic dialysis, CMV-positive cells were found in specimens from 53% of the transplant recipients and 28% of the patients on chronic dialysis. The HHV-6B positive cells were found in the colonic mucosa specimens from 36% of the transplant recipients and 22% of the patients on chronic dialysis, CMV-positive cells were found in specimens from 36% of the transplant recipients and 17% of the patients on chronic dialysis. The HHV-6B positive cells were found equally often in the gastroduodenal as in the colorectal mucosa. The HHV-6B positive cells as well as CMV positive cells were simultaneously found in every fifth of transplant recipients.     

Efficacy of single-dose azithromycin in treatment of acute otitis media in children after a baseline tympanocentesis

Children with acute otitis media underwent tympanocentesis and were given a single dose of 30 mg of azithromycin/kg of body weight. At day 28, the overall clinical cure rate was 206 of 242 (85%). Clinical cure rates for patients infected with Streptococcus pneumoniae (67 of 76; 88%) and Haemophilus influenzae (28 of 44; 64%) were consistent with historical rates for the 5-day dosing regimen.     

Human herpesvirus 6 antigenaemia in allogeneic stem cell transplant recipients: impact on clinical course and association with other beta-herpesviruses

Human herpesvirus 6 (HHV-6) antigenaemia was prospectively studied in 58 adult allogeneic stem cell transplant (SCT) recipients. Altogether 42 of 58 recipients (72%) demonstrated HHV-6 specific antigens in peripheral blood mononuclear cells after SCT, 22 of 36 (61%) when the donor was a sibling and 20 of 22 (91%) when the donor was unrelated. The cumulative incidence of HHV-6A, HHV-6B, HHV-7, and cytomegalovirus antigenaemia during the first 6 months after SCT was 33%, 62%, 44% and 63% respectively. The median day of the onset of each antigenaemia was +24, +4, +59, and +46 after SCT respectively. There were no clinical findings related to HHV-6A and HHV-7 antigenaemias. A rash was diagnosed in 10 of 38 (26%) HHV-6B antigenaemia positive patients during the first month after SCT compared with one of 20 (5%) HHV-6B negative patients. Of the HHV-6B antigenaemia cases, six of 10 rashes were treated as acute graft-versus-host disease (GVHD) and four of 10 were considered to be of a viral origin. Fifteen patients had acute GVHD diagnosed. Acute GVHD manifested statistically significantly (P = 0.034) earlier in the nine patients with HHV-6B antigenaemia compared with the six patients who were HHV-6B negative.     

HHV‐6 in liver transplantation: A literature review

Human herpesvirus 6 (HHV‐6A and HHV‐6B) can cause primary infection or reactivate from latency in liver transplant recipients, which can result in a variety of clinical syndromes, including fever, hepatitis, encephalitis and higher rates of graft dysfunction as well as indirect effects including increased risks of mortality, CMV disease, hepatitis C progression and greater fibrosis scores. Although HHV‐6 infection is currently diagnosed by quantifying viral DNA in plasma or blood, biopsy to demonstrate histopathological effects of HHV‐6 remains the gold standard for diagnosis of end‐organ disease. HHV‐6 reactivation may be restricted to the infected organ with no evidence of active infection in the blood. HHV‐6 infections in liver transplant patients are mostly asymptomatic, but clinically significant tissue‐invasive infections have been treated successfully with ganciclovir, foscarnet or cidofovir. Inherited chromosomally integrated HHV‐6 (ciHHV‐6), in either the recipient or the donor organ, may create confusion about systemic HHV‐6 infection. Recipients with inherited ciHHV‐6 may have an increased risk of opportunistic infection and graft rejection. This article reviews the current scientific data on the clinical effects, risk factors, pathogenesis, diagnosis and treatment of HHV‐6 infections in liver transplant recipients.     

Acute childhood bacterial meningitis in Luanda, Angola

Incidence, morbidity and mortality of bacterial meningitis in developing countries are manifold greater than those in the industrialized world. We reviewed retrospectively children with meningitis treated in the paediatric hospital of Luanda in 2004. Among the 555 children, median age 11.0 months, the leading agents were Haemophilus influenzae type b (Hib), pneumococcus, and meningococcus in 60%, 24%, and 10%, respectively. The median length of illness before admission was 7 d. 65% had convulsed. Altered level of consciousness was observed in 61% and blood haemoglobin lower than 8 g/dl in 36% of cases. Case fatality was 35% and, of survivors, 24% were left with severe neurological sequelae. Blood transfusion appeared beneficial since fatality of children with and without transfusion was 23% versus 39% (p=0.003). While awaiting large-scale vaccinations, tools to improve the prognosis of meningitis in Angola comprise generating better awareness to reduce the delay, better fluid treatment and monitoring and active use of blood transfusions.     

A vaccine targeting angiomotin induces an antibody response which alters tumor vessel permeability and hampers the growth of established tumors

Angiomotin (Amot) is one of several identified angiostatin receptors expressed by the endothelia of angiogenic tissues. We have shown that a DNA vaccine targeting Amot overcome immune tolerance and induce an antibody response that hampers the progression of incipient tumors. Following our observation of increased Amot expression on tumor endothelia concomitant with the progression from pre-neoplastic lesions to full-fledged carcinoma, we evaluated the effect of anti-Amot vaccination on clinically evident tumors. Electroporation of plasmid coding for the human Amot (pAmot) significantly delayed the progression both of autochthonous tumors in cancer prone BALB-neuT and PyMT genetically engineered mice and transplantable TUBO tumor in wild-type BALB/c mice. The intensity of the inhibition directly correlated with the titer of anti-Amot antibodies induced by the vaccine. Tumor inhibition was associated with an increase of vessels diameter with the formation of lacunar spaces, increase in vessel permeability, massive tumor perivascular necrosis and an effective epitope spreading that induces an immune response against other tumor associated antigens. Greater tumor vessel permeability also markedly enhances the antitumor effect of doxorubicin. These data provide a rationale for the development of novel anticancer treatments based on anti-Amot vaccination in conjunction with chemotherapy regimens.     

The Effects of Formula Feeding on Physiological and Immunological Parameters in the Gut of Neonatal Rats

A unique model of formula feeding in the neonatal rat was utilized to investigate the effects of an enterally delivered artificial milk formula on clinically relevant immunological and biological characteristics in the gut, compared to naturally reared pups. Hooded Wistar rat pups were randomly allocated to two treatment groups: formula-fed (FF) or naturally suckled (NS). A flexible silastic intra-gastric cannula was surgically implanted into the FF pups, through which an artificial rat milk supplement was continuously delivered from day 4 to day 10 of life. Rat pups were sacrificed at 10 days of age. Body weight, small intestinal weight, mucosal CD8⁺ cell numbers, and ileal lactase activity in FF animals were significantly decreased compared to their NS counterparts (P < 0.05). Numbers of eosinophils, mucosal mast cells, CD4⁺ T-cells, ileal villus height and gastric emptying times were significantly increased in FF pups (P < 0.05). We have developed a new rat model of artificial feeding which possesses important immunological and biological similarities to the premature human infant.