Anaemia during pregnancy in southern Tanzania

Anaemia in pregnancy is associated with maternal morbidity and mortality and is a risk factor for low birth-weight. Of 507 pregnant women recruited in a community, cross-sectional study in southern Tanzania, 11% were severely anaemic (<8 g haemoglobin/dl). High malarial parasitaemia [odds ratio (OR)=2.3] and iron deficiency (OR=2.4) were independent determinants of anaemia. Never having been married (OR=2.9) was the most important socio-economic predictor of severe anaemia. A subject recruited in the late dry season was six times more likely to be severely anaemic than a subject recruited in the early dry season. Compared with the women who were not identified as severely anaemic, the women with severe anaemia were more likely to present at mother-and-child-health (MCH) clinics early in the pregnancy, to seek medical attention beyond the MCH clinics, and to report concerns about their own health. Pregnancy-related food taboos in the study area principally restrict the consumption of fish and meat. Effective anti-malaria and iron-supplementation interventions are available but are not currently in place; improvements in the mechanisms for the delivery of such interventions are urgently required. Additionally, opportunities for contacting the target groups beyond the clinic environment need to be developed.     

Rapid receptor-proximal signaling assays for FcR gamma-containing receptors

Novel, cell-based assays, based on bioluminescence resonance energy transfer, have been developed for FcepsilonRI- and GPVI-FcRgamma complex-mediated signaling at receptor-proximal steps. In a stable transfectant of the HEK-293 cell line expressing human FcepsilonRIalpha, FcepsilonRIbeta, and FcRgamma-GFP2 and Syk(1-265)-Rluc fusion proteins, FcepsilonRI cross-linking markedly increased BRET2 ratios, which are the ratios of GFP2 emission to Rluc emission. These ratios reflect the FcRgamma-GFP2-Syk(1-265)-Rluc interaction in living cells. The signals are specifically inhibited by the Src-family kinase inhibitor PP2. Separately, in transient transfectants expressing GPVI, FcRgamma-GFP2, and Syk(1-265)-Rluc, the GPVI-specific ligand convulxin induced a two-fold increase in the BRET2 ratio and this increase was also inhibited by PP2. Finally, a differential assay was developed which permits the measurement of FcepsilonRI- and GPVI-FcRgamma complex-mediated signaling in the same cell. These assays provide useful methods for monitoring FcRgamma-Syk interaction in real time in living cells and may contribute to the understanding of signal regulation through FcRgamma-containing receptors.     

Development of a cell-free binding assay for rat ICAM-1/LFA-1 interactions using a novel anti-rat LFA-1 monoclonal antibody and comparison with a cell-based assay.

The importance of the interaction between lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) in the progression of inflammatory responses in vivo has been demonstrated mainly in rats. The present study was undertaken to develop binding assays suitable for measuring the rat ICAM-1/LFA-1 interaction in vitro. We first examined binding of rat T lymphoma FTL43 cells, which express LFA-1, to immobilized rat ICAM-1. Although FTL43 cells bound avidly to immobilized ICAM-1 and the binding was abolished with anti-LFA-1 monoclonal antibodies (mAbs), the binding was not completely inhibited by most anti-ICAM-1 mAbs. We next purified rat LFA-1 from FTL43 cells and constructed a cell-free binding assay. By using a newly developed anti-rat LFA-1 mAb RL14/9, which does not inhibit ICAM-1/LFA-1 interactions, binding of purified rat LFA-1 to immobilized ICAM-1 was successfully detected, whereas only a low signal to noise ratio was observed when binding of ICAM-1 to immobilized LFA-1 was examined. Moreover, we found that simultaneous addition of purified LFA-1 and biotinylated RL14/9 to ICAM-1-coated wells resulted in more sensitive detection of rat ICAM-1/LFA-1 binding. The binding was completely blocked with both anti-LFA-1 and anti-ICAM-1 mAbs and was much more sensitive to inhibition by the ICAM-1-IgG chimera, as compared with the cell-based assay. These results indicate that the cell-free binding assay provides a rapid and sensitive method for screening rat ICAM-1/LFA-1 antagonists, whose therapeutic effect on inflammatory diseases can further be evaluated in vivo.     

Enhanced oxidative stress contributes to worse prognosis and delayed neurofunctional recovery after striatal intracerebral hemorrhage in 5XFAD mice

Although Alzheimer's disease (AD) is associated with an increased risk of intracerebral hemorrhage (ICH) caused by hypertension and cerebral amyloid angiopathy, the precise clinical course after hypertensive ICH in AD patients is still unknown. In this study, we investigated how striatal ICH, a frequent site for hypertensive ICH, affected the prognosis of AD. We employed 17‐ and 18‐month‐old male 5XFAD (5X) mice and littermate (LT) controls, and striatal ICH was induced by collagenase injection. First, to address the acute effects of ICH on 5X mice, hemorrhagic volume and brain edema were evaluated 3 days after ICH. Next, to address the long‐term effects of ICH on 5X mice, morbidity, mortality, neurological function (beam‐walking and rotarod tests), and cognitive function (Y‐maze and nest‐building tests) were monitored. Twenty‐eight days later, the animals were euthanized, their brains were isolated, and the cytotoxic alterations were investigated. The results revealed that the acute effects of ICH were not significantly different between 5X and LT mice. In contrast, 5X mice showed significantly higher morbidity and mortality in response to ICH, as well as delayed neurological function recovery, compared to LT mice through 28 days. ICH did not affect cognitive function in either group. Infiltrated macrophages in the perihemorrhagic cortex, gp91^phox, p67^phox, and COX‐2 were significantly increased in 5X mice in response to ICH. We demonstrated that striatal ICH deteriorated prognosis and delayed neurofunctional recovery in 5X mice, which might be associated with enhanced oxidative stress in the presence of AD‐like pathology.     

Comparison of pregnancy and labour in teenagers and primigravidas aged 21-25 years in Transkei.

The outcome of pregnancy and labour in 601 primigravidas aged 19 years and under was compared with that of 221 primigravidas aged 21-25 years. The risks of antenatal complications, such as anaemia, haemorrhage and pre-eclampsia, were the same in both groups. The much-published low birth weight of babies born to teenagers was not observed; the weights of the babies in the two groups were similar. The caesarean section rates of 12% and 15% for the study and control groups, respectively, compared very well with the rate in the general obstetric population, indicating that the risk of cephalopelvic disproportion (the commonest indication for caesarean section) is the same among all primigravidas, whatever their age. The perinatal mortality rate was, however, slightly higher among the teenagers (58,2/1,000) than among the older mothers (40,7/1,000), although the difference was not statistically significant. Therefore the notion held by many people who practise midwifery that teenage mothers are, because of their age alone, more disadvantaged in terms of obstetric performance, is not absolutely true.     

New experimental model for adoptive transfer of murine autoimmune orchitis

Previous studies demonstrated that experimental autoimmune orchitis (EAO) was produced in C3H/He mice with very high incidence by subcutaneous (s.c.) injections of viable syngeneic testicular germ cells (TC), without resorting to any adjuvants or immunopotentiators. Using this EAO model, a new and simple protocol was developed for adoptive transfer of EAO. Cell donors were C3H/He mice that received s.c. injections twice with TC alone. Spleen cells from the donors were stimulated in vitro with TC, propagated in interleukin-2 containing medium, then injected i.p. to naive recipient mice. This procedure induced severe orchitis and hypospermatogenesis with or without inflammation in epididymis and vas deferens in the recipients at high incidence. Elimination of all T cells or CD4+ T cells before the transfer produced no histopathological signs in the recipients whereas that of the CD8+ T cells or B cells had no inhibitory effect on the disease transfer, indicating that the effector cells are CD4+ T cells.     

Bezafibrate alone is an effective first-line therapy for primary sclerosing cholangitis: a case report]

The patient was a 58-year-old female. Though she had been in good health, increased hepatobiliary enzymes were detected in a health examination. She visited our hospital for close examination. The serum IgG4 level was normal, but ERCP and MRCP showed band-like stricture and beaded appearance of the bile ducts. A diagnosis of primary sclerosing cholangitis (PSC) was made. Since hyperlipidemia was also observed, oral administration of bezafibrate (400mg/day) alone was performed as the initial treatment, and transaminase, ALP, and GGT rapidly decreased. These results suggested that the initial administration of bezafibrate alone is effective against PSC.     

180. Zur Organkonservierung der Niere und Langzeitperfusion der Leber

Zusammenfassung Zur Verlängerung der Ischämietoleranz der Niere und anderer Organe wird eine Überdruck-Konservierungskammer nach klinischer Prüfung empfohlen. Die aus Plexiglas bestehende Kammer läßt einen Überdruck bis 8 atü zu und garantiert eine Temperaturkonstanz von 2–4°C. Im Deckel ist ein Druckmanometer, ein Einfüllstutzen und ein Reduzierventil sowie ein Thermofühler installiert. Sie wird als Transport-Konservierungskammer empfohlen, da dadurch die Hypothermie und gleichzeitige hyperbare Oxygenation Konservierungszeiten auch in der Humanmedizin bei der Transplantation der Niere von 8–11 Std möglich sind.Außerdem wird ein Organperfusionssystem vorgestellt, bestehend aus einer Herz-Lungenmaschine mit einer pulsatorischen Pumpe (A. hepatica) und zwei Rollerpumpen (Pfortader), einem Bubble-Oxygenator und Heat-Exchanger sowie der Organperfusionskammer, mit deren Hilfe und einem Überdruck von 1/2–11/2 ata Perfilsionszeiten von 30–34 Std unter Hypothermie von 14°C ermöglicht werden. Voraussetzung ist, daß die Leber schon im Spenderorganismus während des Auswaschens (15–20 min) zur Vermeidung primärer Hypoxieschäden unter 20°C abgekühlt und dann erst auf die Perfusion mit der nicht Hb-haltigen Lösung umgeschaltet wird. Eine wechselnde und rhythmische Druckänderung von 1/2 ata wird als besonders wesentlich erachtet.Durch die Kontrolle des Übertritts der Indizenzyme der Leber GLDH und GOT >4,0 mU/ml, LDH >180 mU/ml ins Perfusat und die aktive Ausscheidung von Bengal-Rosa, Messung des Lactatspiegels und des Sauerstoffverbrauches wird die Funktionstüchtigkeit bewiesen während der Langzeitperfusion. Die Leistungsfähigkeit eines derartig hypotherm und hyperbar konservierten und perfundierten Organs wird beim heterologen Leberersatz des Menschen im Coma hepaticum demonstriert.

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Summary To lengthen ischaemia tolerance of the kidney and other organs an excess pressure preservation chamber is recommended after clinical tests. The chamber consists of plexiglass, permits an excess pressure of 8 kg/cm² and ensures a constant temperature of 2–4°C. In the lid there is a pressure gauge, a filling socket and a reducing valve as well as a thermostat. A portable preservation chamber is recommended since, owing to hypothermia and simultaneous hyperbaric oxygenation, preservation periods of 8–11 hours are possible in kidney transplantation even in human surgery. In addition, an organ perfusion system is presented, consisting of a heart-lung machine with a pulsatory pump (hepatic artery) and two roller pumps (portal vein), a bubble oxygenator and heat exchanger as well as the organ perfusion chamber with the aid of which and with an excess pressure of 1/2 to 11/2 kg/cm² perfusion periods of 30–40 hours are possible under hypothermia of 14°C. It is necessary that the liver still in the donor's body is cooled below 20°C during washing-out (15–20 min), to prevent primary hypoxia damage, and that it is only then switched over to perfusion with Hb-free solution. Alternating and rhythmic pressure changes of 1/2 kg/cm² are considered especially important. Functional efficiency during long-term perfusion is confirmed by checking the passage of the characteristic liver enzymes (GLDH and GOT >4.0 mU/ml, LDH >180 mU/ml) into the perfusion solution, the active excretion of bengal-rose, measuring the lactate level and oxygen consumption. The performance of an organ preserved hypothermally and hyperbarically and perfused in this manner is demonstrated in heterologius liver replacement in man in hepatic coma.