Monitoring oxypurines levels in women with pregnancy induced hypertension and in women with physiological pregnancy

We report on catamnestic and clinical results of a 18-24 month follow-up study of 65 alcohol-dependent patients who in 1992-1994 took part in an 8-month outpatient treatment programme. The psychotherapeutic concept of this treatment facility is described. 51 of the 65 patients who had participated in the programme could be subsequently personally interviewed, 7 patients refused to take part, 6 could not be reached and 1 had died. 40 of the 51 patients had properly completed the outpatient treatment. Assuming that all patients who could not be interviewed or refused, were relapsers the abstinence rate was found to be 48% (n = 31). Although selective factors may contribute to this result, the clinical findings so far seem to indicate that outpatient treatment for alcoholics is a promising new therapeutic approach in the treatment of alcoholism. Further studies are needed to assess the possible benefits and the indications for this outpatient treatment in greater detail.     

Oral low-dose magnesium gluconate preventing pregnancy induced hypertension

OBJECTIVE: To study the effects of oral low-dose magnesium gluconate in prevention of pregnancy induced hypertension (PIH) and its mechanism. METHODS: A prospective randomized double-blind study was carried out in 51 pregnant women as treatment group (including 22 cases as treatment group 1 and 29 cases as treatment group 2) and 51 pregnant women as controls (including 28 cases as controls group 1 and 23 cases as control group 2). Low-dose magnesium gluconate (3 g/day) or placebo was given from the 28th week of gestation to delivery consecutively. RESULTS: 4% of the pregnant women developed PIH after magnesium gluconate treatment, which was substantially lower than that in the control group (16%) (P < 0.05). In the treatment group 2, women showed higher concentration of 6-keto-prostaglandin F1 alpha (PGF1a) and 6-keto-/thromboxane B2(TXB2) (P/T) ratio than that of the control group 2. Moreover, TXB2 level was lower than that in the control group 2. In the treatment group 1 women showed higher ratio of P/T than that of the control group 1. There were no significant differences of serum magnesium concentration among all groups. CONCLUSION: Low-dose magnesium gluconate may efficiently prevent PIH in high risk women. The mechanism of action of magnesium gluconate probably involves to keep the balance of PGI2 and TXA2, but not associates with serum magnesium level.     

Immunoglobulin levels in psychiatric patients

In a study of 19 schizophrenic patients, 7 nonschizophrenic patients, and 31 controls, the authors found significantly higher mean serum levels of 1) immunoglobulin A in schizophrenic women then in control women and in schizophrenic blacks than in either schizophrenic whites or black controls. 2) immunoglobulin D in schizophrenic blacks than in schizophrenic whites, 3) immunoglobulin M in controls than in nonschizophrenic patients, and 4) immunoglobulin G (IgG) in schizophrenics whose urine was positive for phenothiazines than in schizophrenics whose urine was negative for phenothiazines. High serum levels of IgG were associated with no or mild hallucinations and low levels with moderate or severe hallucinations. Black female patients had significantly more severe hallucinaions than white female patients. The authors discuss the possible implications of these findings.     

Hemoglobin A1c in diabetes related to pregnancy induced hypertension

OBJECTIVE: To test the hypothesis that the poor control of diabetes during pregnancy is correlated with a high rate of pregnancy induced hypertension (PIH). METHODS: A retrospective analysis on 146 pregnant women with diabetes mellitus of White's class B to RF (gestational diabetes was excluded) diagnosed before pregnancy was carried out in Yale-New Haven hospital, U.S.A. RESULTS: 36.3% of the diabetic women developed PIH. Hemoglobin A1c (HbA1c) levels were higher than normal in 63.7% (93 cases) of the patients during their initial prenatal visits. In the group with HbA1c score > or = 6 and White's Class D-RF, more cases developed PIH than that in groups with HbA1c score < 6 and White's Class B and C (P < 0.01, P < 0.05). CONCLUSION: Diabetic women with high HbA1c score or advanced White's Class during pregnancy were at increased risk for PIH. Good control of blood glucose level throughout pregnancy may reduce the risk of PIH in diabetic women.     

Glycosylated high density lipoprotein in diabetes related to pregnancy induced hypertension

OBJECTIVE: To investigate the glycosylation of high density lipoprotein (glc-HDL) and its specific binding to human lung fibroblasts (HLF) receptors in gestational diabetes woman and to study its relationship with pregnancy induced hypertension (PIH). METHODS: The glc-HDL was measured by fluorimetry and the specific binding of HDL to HLF receptors was measured with enzyme linked immunoreceptor assay in 32 gestational diabetic woman group 1, 34 group II, 36 normal pregnant (NP) and 32 normal non-pregnant (NNP) women. RESULTS: The levels of glc-HDL and the intracellular total cholesterol in diabetic pregnant woman group I and II were significantly higher than those in the NP and the NNP (P < 0.01). The cell binding, internalization and degradation of glc-HDL were higher than that in the NP and the NNP. CONCLUSION: The change of HDL level and lipid deposition during the process may be one of the causes for arteriole spasm in PIH.     

Clinical significance of changes of urinary enzymes in pregnancy induced hypertension

OBJECTIVE: To study the clinical significance of changes of N-acetyl-beta-D-glucosaminidase (NAG) and lysozyme in random urine sample in pregnancy induced hypertension (PIH). METHODS: The concentration of NAG was measured by oronitrophenol spectrophotometric methods, and the concentration of lysozyme by agar plate diffusion method. Random urine samples from 266 pregnant women were examined, 110 cases were normal pregnant women, 156 cases were PIH patients. RESULTS: (1) The level of NAG and lysozyme in moderate and severe PIH patients were significantly higher than that in mild PIH patients and normal pregnant women (P < 0.01) and it increased with the severity of disease. (2) There was a positive correlation between NAG and protein/creatinine (Pr/Cr) ratio in random urine. (3) There was a positive correlation between urinary lysozyme and serum beta 2-microglobulin (r = 0.874, P < 0.05). CONCLUSION: Determination of urinary NAG and lysozyme levels will differentiate various states of PIH.     

Multiple forms of complement C3 in trout that differ in binding to complement activators

In all other species analyzed to date, the functionally active form of complement component C3 exists as the product of a single gene. We have now identified and characterized three functional C3 proteins (C3-1, C3-3, and C3-4) in trout that are the products of at least two distinct C3 genes. All three proteins are composed of an alpha-and a beta-chain and contain a thioester bond in the alpha-chain. However, they differ in their electrophoretic mobility, glycosylation, reactivity with monospecific C3 antibodies, and relative ability to bind to various surfaces (zymosan, Escherichia coli, erythrocytes). A comparison of the partial amino acid sequences of the three proteins showed that the amino acid sequence identity/similarity of C3-3 to C3-4 is 87/91%, while that of C3-3 and C3-4 to C3-1 is 51.5/65.5% and 60/73% respectively. Thus, trout possess multiple forms of functional C3 that represent the products of several distinct genes and differ in their ability to bind covalently to various complement activators.     

Low immunoglobulin G3 levels in wheezy children

This study aimed to investigate the prevalence of IgG subclass deficiency in wheezy children aged <3 y. Serum levels of IgA, IgE and IgG subclasses were measured in 310 children with recurrent wheezing and in 100 healthy controls. IgG3 levels were below the normal lower limit in 123 (39.6%) patients. This finding may reflect delayed maturation of the immune system, predisposing young children <3 y of age to wheezing.     

The changes of plasma nitric oxide in patients with pregnancy induced hypertension

OBJECTIVE: To determine whether the antepartum and postpartum plasma nitric oxide (NO) levels were changed in pregnancy induced hypertension (PIH). METHODS: 30 patients with PIH and 30 healthy women in their late pregnancy were studied. The antepartum and postpartum plasma NO2-/NO2- levels, the stable metabolic end products of NO, and cyclic guanosine monophosphate (cGMP) were measured with greiss reagent. RESULTS: (1) The plasma concentration of NO2-/NO2- and cGMP in patients with PIH decreased significantly when compared with that of healthy pregnant women (P < 0.01). (2) The concentration of antepartum plasma NO2-/NO2- was markedly lower than that of postpartum one in PIH patients (P < 0.01). (3) There was a negative correlation between the plasma NO2-/NO3- level and systolic blood pressure in PIH (P < 0.01). (4) A positive correlation was seen between plasma NO2-/NO3- levels and cGMP levels in PIH patients (P < 0.01). CONCLUSION: The decrease of NO synthesis may be one of the important factors responsible for PIH.     

The covalent binding reaction of complement component C3

The covalent binding of C3 to target molecules on the surfaces of pathogens is crucial in most complement-mediated activities. When C3 is activated, the acyl group is transferred from the sulfhydryl of the internal thioester to the hydroxyl group of the acceptor molecule; consequently, C3 is bound to the acceptor surface by an ester bond. It has been determined that the binding reaction of the B isotype of human C4 uses a two-step mechanism. Upon activation, a His residue first attacks the internal thioester to form an acyl-imidazole bond. The freed thiolate anion of the Cys residue of the thioester then acts as a base to catalyze the transfer of the acyl group from the imidazole to the hydroxyl group of the acceptor molecule. In this article, we present results which indicate that this two-step reaction mechanism also occurs in C3.     

Radioimmunoassay of plasma endothelin in maternal and fetal umbilical cord vein in pregnancy induced hypertension

Endothelin (ET) level was measured in 48 cases of normal pregnancies and in 29 cases of pregnancy induced hypertension (PIH) by radioimmunoassay (RIA). The results indicate that the difference of ET values between maternal and fetal umbilical cord vein was nonsignificant in normal pregnancy. Though a slight increase in maternal ET level was found in mild and moderate PIH, however the difference was nonsignificant when compared with normal pregnancy. ET increased significantly in plasma of patients with severe PIH. ET levels of fetal umbilical cord vein in different groups showed no much change. It suggests that ET increasing in plasma of patients with PIH may play a role in pathogenesis of PIH.     

Impaired mast cell-dependent natural immunity in complement C3-deficient mice

The complement system is widely regarded as essential for normal inflammation, not least because of its ability to activate mast cells. However, recent studies have called into question the importance of complement in several examples of mast cell-dependent inflammatory responses. To investigate the role of complement in mast cell-dependent natural immunity, we examined the responses of complement-deficient mice to caecal ligation and puncture, a model of acute septic peritonitis that is dependent on mast cells and tumour necrosis factor-alpha (TNF-alpha). We found that C4- or C3-deficient mice were much more sensitive to caecal ligation and puncture than wild-type (WT) controls (100% versus 20% in 24-h mortality, respectively). C3-deficient mice also exhibited reductions in peritoneal mast cell degranulation, production of TNF-alpha, neutrophil infiltration and clearance of bacteria. Treating the C3-deficient mice with purified C3 protein enhanced activation of peritoneal mast cells, TNF-alpha production, neutrophil recruitment, opsonophagocytosis of bacteria and resistance to caecal ligation and puncture, confirming that the defects were complement-dependent. These results provide formal evidence that complement activation is essential for the full expression of innate immunity in this mast cell-dependent model of bacterial infection.     

Mannan-specific immunoglobulin G antibodies in normal human serum accelerate binding of C3 to Candida albicans via the alternative complement pathway

Candida albicans activates the classical and alternative complement pathways, leading to deposition of opsonic complement fragments on the cell surface. Our previous studies found that antimannan immunoglobulin G (IgG) in normal human serum (NHS) allows C. albicans to initiate the classical pathway. The purpose of this study was to determine whether antimannan IgG also plays a role in initiation of the alternative pathway. Pooled NHS was rendered free of classical pathway activity by chelation of serum Ca2+ with EGTA alone or in combination with immunoaffinity removal of antimannan antibodies. Kinetic analysis revealed a 6-min lag in detection of C3 binding to C. albicans incubated in EGTA-chelated NHS, compared to a 12-min lag in NHS that was both EGTA chelated and mannan absorbed. The 12-min lag was shortened to 6 min by addition of affinity-purified antimannan IgG. The accelerating effect of antimannan IgG on alternative pathway initiation was dose dependent and was reproduced in a complement binding reaction consisting of six purified proteins of the alternative pathway. Both Fab and F(ab')2 fragments of antimannan IgG facilitated alternative pathway initiation in a manner similar to that observed with intact antibody. Immunofluorescence analysis showed that addition of antimannan IgG to EGTA-chelated and mannan-absorbed serum promoted an early deposition of C3 molecules on the yeast cells but had little or no effect on distribution of the cellular sites for C3 activation. Thus, antimannan IgG antibodies play an important regulatory role in interactions between the host complement system and C. albicans.     

Status of free radicals and their scavenging enzymes in pregnancy induced hypertension (PIH)

The levels of lipid peroxidation (malonaldialdehyde), one of the consequence of free radical damage, and the antioxidant enzymes superoxide dismutase and catalase were estimated in the blood samples of fourteen normal and thirteen pregnancy induced hypertensive patients. A marked increase in malonaldialdehyde (p < 0.001) with concomitant decrease in superoxide dismutase (p < 0.001), catalase (p < 0.001) activities were observed in PIH as compared to normal pregnancy, thereby indicating the involvement of free radicals in PIH.     

X-ray crystal structure of C3d: a C3 fragment and ligand for complement receptor 2

Activation and covalent attachment of complement component C3 to pathogens is the key step in complement-mediated host defense. Additionally, the antigen-bound C3d fragment interacts with complement receptor 2 (CR2; also known as CD21) on B cells and thereby contributes to the initiation of an acquired humoral response. The x-ray crystal structure of human C3d solved at 2.0 angstroms resolution reveals an alpha-alpha barrel with the residues responsible for thioester formation and covalent attachment at one end and an acidic pocket at the other. The structure supports a model whereby the transition of native C3 to its functionally active state involves the disruption of a complementary domain interface and provides insight into the basis for the interaction between C3d and CR2.     

A bispecific monoclonal antibody directed against both the membrane-bound complement regulator CD55 and the renal tumor-associated antigen G250 enhances C3 deposition and tumor cell lysis by complement

Tumor cells may inhibit the induction of a complement-mediated inflammatory response through overexpression of membrane-bound regulators of complement activation. Therefore, it is of interest to determine the most efficient approach to block these membrane-bound complement regulators on tumor cells. In the present study, we first generated a bispecific mAb directed against both CD55, using the functional blocking mAb MBC1, and the highly expressed HLA class I molecule as a model for a tumor-associated Ag, using the mAb W6/32. Tumor cells opsonized with bispecific mAb W6/32*MBC1, then exposed to complement and subsequently stained for C3 deposition, were assessed by flow cytometric analysis. We found that opsonization with W6/32*MBC1 resulted in a 92% enhancement of C3 deposition on renal tumor cells as compared with opsonization with W6/32 alone and a 17% enhancement of the C3 deposition as compared with incubation with a mixture of both parental mAb. Based on these results, we developed a bispecific mAb recognizing both CD55 and the relatively low expressed renal tumor-associated Ag G250. Increasing concentrations of the bispecific mAb G250*MBC1 resulted in a 25 to 400% increase in C3 deposition on renal tumor cells as compared with C3 deposition in the presence of the parental mAb G250 alone. G250*MBC1 enhanced C3 deposition by 21% in comparison with a mixture of both parentals. Furthermore, opsonization of tumor cells with G250*MBC1 rendered these cells more sensitive to complement-mediated lysis. In conclusion, the bispecific mAb G250*MBC1 induces deposition of C3 and tumor cell lysis more efficiently than G250 alone.