[Attitude toward sexual health education and its correlates among community-based older adults in Shanghai].

Objective: To understand the attitudes toward sexual health education and its correlates among community-based older adults in Shanghai, China. Methods: From June 2020 to December 2022, a cross-sectional survey was conducted among community residents aged ≥50 in Shanghai through multi-stage sampling. The estimated sample size was 735. The questionnaire included sociodemographic characteristics, health characteristics, and history of sexual health education. The multivariable logistic regression model was used to assess the correlates of attitudes toward sexual health education among community-based older adults. Results: A total of 824 participants (489 males and 335 females) with age of (65.1±8.1) years were included, whose main age distribution was 60-69 years (45.3%). The prevalence of supporting sexual health education among older adults was 49.4% (45.2% of men and 55.5% of women). Males (aOR=0.61, 95%CI: 0.44-0.83), aged 70 years and older (aOR=0.62, 95%CI: 0.40-0.94), urban residents (aOR= 2.54, 95%CI: 1.81-3.58), self-reported very good or excellent health status (aOR=1.64,95%CI: 1.04-2.58), having depressive symptoms (aOR=0.37,95%CI: 0.15-0.85), and having a history of sexual health education (aOR=8.64,95%CI: 4.62-17.70) were associated with their attitude toward sexual health education. Conclusions: The proportion of community-based older adults in Shanghai who support sexual health education was not high. Their attitudes toward sexual health education were associated with their self-reported health status, depressive symptoms, and history of sex education. Health professionals and institutions should focus on community-based older adults with key characteristics and tailor interventions to promote the willingness to receive sexual health education among older adults in China and to promote the popularity of sexual health education in this population.

[Condom use and its correlates among community-based older adults in Chongqing].

Objective: To understand the current status of condom use and its correlates among community-based older adults in Chongqing, China. Methods: Cross-sectional study based on a multistage sampling method was conducted in Chongqing from June 2020 to December 2022. The estimated sample size was 735. Through face-to-face interviews, the investigators collected the sociodemographic characteristics, sexual behavior characteristics, awareness of AIDS prevention knowledge, etc. A multivariable logistic regression model was used to explore the correlates of condom use during the last sexual behavior among the participants. Results: A total of 761 participants were included in this study, with 476 males and 285 females, whose average age was (63.8±8.2) years old, mainly in the age group of 60-69 years (44.5%). Among the participants, the rate of condom use during the last sexual behavior was 9.7%. The multivariable logistic regression analysis indicated that correlates of condom use during the last sexual behavior included urban household registration (aOR=2.34, 95%CI: 1.12-4.89), monthly income of 1 000-4 999 Yuan, and 5 000 Yuan and above (aOR=4.49, 95%CI: 1.31-15.41; aOR=16.33, 95%CI: 4.30-62.00), self-assessed sexual behavior risk as very risky/relatively risky (aOR=3.97, 95%CI: 1.40-11.31), awareness of AIDS prevention knowledge (aOR=0.36, 95%CI: 0.21-0.62). Conclusions: The rate of condom use among community-based older adults in Chongqing is low. Comprehensive intervention measures should be taken in combination with the characteristics and needs of community-based older adults to improve awareness of AIDS prevention knowledge and perception of AIDS risk and promote condom use among this population.

[Sexually active status and its correlates among community-based older adults in Tianjin].

Objective: To understand the sexually active status among community-based older adults aged ≥50 years in Tianjin, China, and to explore the potential correlates. Methods: A cross-sectional survey using multistage sampling among community-based older adults aged ≥50 was conducted between June 2020 and December 2022. The estimated sample size was 735. The survey collected questionnaire information through face-to-face interviews with investigators, including sociodemographic, health, and sexual lifestyle characteristics. The multivariable logistic regression model was used to assess correlates of sexually active status. Results: A total of 776 study participants (510 males and 266 females) were included, whose major age distribution was 50-59 years (45.9%). The overall sexual activity prevalence of the participants was 45.6%. Older age (60-69: aOR=0.67, 95%CI: 0.45-0.99; ≥70: aOR=0.12, 95%CI: 0.07-0.21), being male (aOR=1.93, 95%CI: 1.32-2.82), living in urban area (aOR=0.18, 95%CI: 0.12-0.28), living with spouse/married (aOR=2.80, 95%CI: 1.41-5.58), living alone (aOR=0.51, 95%CI: 0.27-0.96), having difficulty climbing stairs or walking (aOR=0.55, 95%CI: 0.31-0.97), having chronic diseases (one chronic disease: aOR=0.55, 95%CI: 0.36-0.85; two or more chronic diseases: aOR=0.53, 95%CI: 0.33-0.84) were associated with sexually active status among older adults. Conclusions: Many community-based older adults remained sexually active. There was an association between physical health and sexually active status among community-based older adults. Incorporating sexual health services into healthcare services for community-based older adults could be advocated, with a concurrent emphasis on enhancing the awareness and competence of providing sexual health services among community-based healthcare workers.

[Association between rs10938397 polymorphism in GNPDA2 and obesity in children at different stages of development].

Objective: To examine the association between rs10938397 polymorphism in glucosamine-6-phosphate deaminase 2 (GNPDA2) and risk of obesity in children at different stages of development and analyze the differences in the association. Methods: A total of 3 503 school-aged children were selected from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study in Beijing and their complete anthropometry weight, height, fat mass percentage (FMP), fat mass index (FMI) and free fat mass index (FFMI) and sexual maturation (SM) data were used. The developmental stages were evaluated using male testicular volume and female breast Tanner staging. FMP, FM and FFM were measured by bioelectrical impedance analysis. General obesity and adiposity were respectively defined according to Chinese sex-age-specific body mass index (BMI) cutoffs and sex-age-specific FMP cutoffs. The SNP rs10938397 were genotyped by the TaqMan Allelic Discrimination Assay with the GeneAmp 7900 sequence detection system (Applied Biosystems, Foster city, CA, USA). Relationships between rs10938397 polymorphism and BMI, FMP, FMI and FFMI and different types of obesity were tested using multivariate linear regression and logistic regression models. Results: After age adjustment and correction for multiple testing, the rs10938397-G was associated with BMI and risk of general obesity in boys in early puberty (ß=0.328, P=0.001; OR=1.420, 95%CI: 1.126-1.790), and the rs10938397-G was associated with BMI in girls in late puberty (ß=0.266, P=0.001). The associations of GNPDA2 rs10938397-G with FFMI and FMI were observed in boys in early puberty (ß=0.137, P=0.016; ß=0.202, P=0.007) and the associations of rs10938397-G with FMP and FMI were observed in girls in late puberty (ß=0.153, P=0.002; ß=0.168, P=0.001). The rs10938397-G was also associated with adiposity in girls in late puberty (OR=1.339, 95%CI: 1.093-1.637). Conclusion: The rs10938397 polymorphism in GNPDA2 is associated with adiposity in girls, and it is important to use an accurate indicator of obesity in exposing the genuine association between genes and obesity.

[Gene-gene interaction on central obesity in school-aged children in China].

Objective: To investigate possible effect of 6 obesity-associated SNPs in contribution to central obesity and examine whether there is an interaction in the 6 SNPs in the cause of central obesity in school-aged children in China. Methods: A total of 3 502 school-aged children who were included in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) Study were selected, and based on the age and sex specific waist circumference (WC) standards in the BCAMS study, 1 196 central obese cases and 2 306 controls were identified. Genomic DNA was extracted from peripheral blood white cells using the salt fractionation method. A total of 6 single nucleotide polymorphisms (FTO rs9939609, MC4R rs17782313, BDNF rs6265, PCSK1 rs6235, SH2B1 rs4788102, and CSK rs1378942) were genotyped by TaqMan allelic discrimination assays with the GeneAmp 7900 sequence detection system (Applied Biosystems, Foster City, CA, USA). Logistic regression model was used to investigate the association between 6 SNPs and central obesity. Gene-gene interactions among 6 polymorphic loci were analyzed by using the Generalized Multifactor Dimensionality Reduction (GMDR) method, and then logistic regression model was constructed to confirm the best combination of loci identified in the GMDR. Results: After adjusting gender, age, Tanner stage, physical activity and family history of obesity, the FTO rs9939609-A, MC4R rs17782313-C and BDNF rs6265-G alleles were associated with central obesity under additive genetic model (OR=1.24, 95%CI: 1.06-1.45, P=0.008; OR=1.26, 95%CI: 1.11-1.43, P=2.98×10(-4); OR=1.18, 95% CI: 1.06-1.32, P=0.003). GMDR analysis showed a significant gene-gene interaction between MC4R rs17782313 and BDNF rs6265 (P=0.001). The best two-locus combination showed the cross-validation consistency of 10/10 and testing accuracy of 0.539. This interaction showed the maximum consistency and minimum prediction error among all gene-gene interaction models evaluated. Moreover, the combination of MC4R rs17782313-C and BDNF rs6265-G was associated with an increased risk of central obesity after adjustment for gender, age, Tanner stage, physical activity and family history of obesity. Conclusions: Our study showed that FTO rs9939609-A, MC4R rs17782313-C and BDNF rs6265-G alleles were associated with central obesity, and statistical interaction between MC4R rs17782313-C and BDNF rs6265-G increased risk of central obesity in school-aged children in China.

[Association between SEC16B polymorphisms and body mass index variation or risk of obesity: a Meta-analysis].

Objective: To systematically evaluate the associations between SEC16B polymorphisms and body mass index (BMI) or risk of obesity in different ethnic populations. Methods: A literature retrieval was carried out by using Wanfangdata, Chinese National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP databases), PubMed, Embase, Web of Science, NIH GWAS catalog databases to collect the research papers published between 2009 and 2015 on the associations between SEC16B polymorphisms and BMI or risk of obesity. Summary beta estimates (ßs), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength for the BMI analyses and obesity status. Meta-analysis was performed with Stata 12.0 software. Results: Totally 15 papers for rs10913469 and 13 papers for rs543874 were included in this Meta-analysis. Under additive genetic model, rs10913469 and rs543874 in SEC16B gene were positively associated with BMI, and the combined ß was 0.04 (95%CI: 0.03-0.05) and 0.03 (95%CI: 0.02-0.04), respectively, and rs10913469 and rs543874 were also associated with the risk of obesity, and the combined OR was 1.11 (95%CI: 1.08-1.15) and 1.28 (95%CI: 1.20-1.36), respectively. There were no significant differences among subgroups of ethnicity, different age groups and literatures with different quality. Conclusion: rs10913469 and rs543874 in SEC16B gene are significantly associated with BMI and the risk of obesity, and C allele of rs10913469 and G allele of rs543874 increase the risk for obesity in different ethnic populations.

The multidrug resistance of tumour cells was reversed by tetrandrine in vitro and in xenografts derived from human breast adenocarcinoma MCF-7/adr cells.

Multidrug resistance (MDR) is one of the main obstacles limiting the efficacy of chemotherapy treatment of tumours. One of the main causes of MDR is linked to the overexpression of P-glycoprotein (P-gp). This study aimed to characterise tetrandrine (Tet), a potent inhibitor of P-gp mediated MDR. Cytotoxicity was determined by the tetrazolium (MTT) assay. A MCF-7/adr cell xenograft model was established to investigate the effect of Tet on reversing MDR in vivo. Mechanistic experiments were conducted to examine the uptake, efflux and accumulation of doxorubicin (Dox) and Fura-2, and to assess lipid membrane fluidity. Tet potentiated the cytotoxicity of Dox; a 20.4-fold reversal of resistance was achieved in the presence of 2.5 micromol/l of Tet. Accumulation and efflux studies with the P-gp substrates, Dox and Fura-2, demonstrated that Tet inhibited the P-gp-mediated drug efflux. In addition, Tet lowered cell membrane fluidity in a concentration-dependent manner. In mice bearing the MDR MCF-7/adr cell xenografts, coadministration of Tet potentiated the antitumour activity of doxorubicin without a significant increase in toxicity. Tet was an extremely potent MDR modulator both in vitro and in vivo, without apparently enhancing the toxicity of the co-administered drugs. Hence, Tet holds great promise as a MDR modulator for the treatment of P-gp-mediated MDR cancers.

Screening and discovery of novel MDR modifiers from naturally occurring bisbenzylisoquinoline alkaloids.

BACKGROUND: The failure of conventional cancer chemotherapy has been linked to overexpression of a membrane associated P-glycoprotein (P-gp) that acts as an energy-dependent drug efflux pump. A promising strategy to conquer multidrug resistance (MDR) is to develop functional MDR modifiers that can inhibit the activity of P-gp. MATERIALS AND METHODS: We used MTT in combination with other in vitro drug evaluation assays to screen potential MDR modifiers from a series of naturally occurring Bisbenzylisoquinoline Alkaloids (BBIs) that were isolated from natural plants. RESULTS: Our in vitro screening assays indicated that at least six of these natural compounds (FF0019, FF0018, FF0015, FF0014, FF0011 and FF0012) showed potent activities to restore sensitivity of resistant tumor cells, such as MCF-7/adr and KBv200 cells, to many antitumor drugs including doxorubicin and vincristine. Further analyses by measurement of radioactive [3H]-Vincristine indicated that these BBIs increased intracellular drug accumulation in MDR cells, but had little effect on drug-sensitive cells. CONCLUSIONS: These results suggested that the mechanism of these compounds to reverse MDR was associated with the increase in the intracellular drug accumulation through inhibiting the activity of P-gp. Another important feature is that the in vitro cytotoxic effect of these naturally occurring BBIs themselves on tumor cells was very low. Thus, these compounds may possess great promise in being developed into novel MDR modifiers.

Cardiac sympathetic afferent activation provoked by myocardial ischemia and reperfusion. Mechanisms and reflexes.

Cardiac sympathetic afferents are known to reflexly activate the cardiovascular system, leading to increases in blood pressure, heart rate, and myocardial contractile function. During myocardial ischemia, these sensory nerves also transmit the sensation of pain (angina pectoris) and cause tachyarrhythmias. The authors' laboratory has been interested in defining the mechanisms of activation of this neural system during ischemia and reperfusion. During these periods, reactive oxygen species, particularly hydroxyl radicals, are produced from the breakdown of purine metabolites and lead to stimulation of sympathetic (and vagal) ventricular chemosensitive nerve endings. For example, stimulation with hydrogen peroxide leads to a small reflex increase in blood pressure from the predominant sympathetic afferent activation that is reduced by simultaneous activation of cardiac vagal afferents (known to exert predominantly depressor reflexes). Central integration of these two opposing reflexes likely occurs at several regions of the brain stem, including the nucleus tractus solitarii, where neural occlusion occurs during simultaneous cardiac sympathetic and vagal-afferent stimulation. Activation of platelets also appears to play a role during myocardial ischemia, leading to local release of serotonin (5HT), which, through a 5HT3 mechanism, stimulates sympathetic afferents. Finally, regional changes in pH from lactic acid (but not hypercapnia), stimulate ventricular afferents and may activate kallikrein to increase bradykinin (BK), which, in turn, breaks down arachidonic acid to form prostaglandins. Prostaglandins sensitize cardiac sympathetic afferents to BK. Thus, stimulation of cardiac sympathetic afferents during ischemia and reperfusion and the resulting reflex events form a multifactorial process resulting from activation of a number of chemical pathways in the myocardium.

Interleukin-1beta sensitizes abdominal visceral afferents of cats to ischaemia and histamine.

1. Activation of abdominal splanchnic visceral afferents during mesenteric ischaemia induces visceral pain and evokes excitatory cardiovascular responses. Previous studies have shown that interleukin-1beta (IL-1beta) concentration is increased locally in tissues during ischaemia and reperfusion. Local administration of IL-1beta sensitizes somatic afferents to mechanical, thermal and chemical stimulation. Therefore, we hypothesized that IL-1beta stimulates or sensitizes splanchnic visceral afferents to ischaemia and to the action of chemical stimuli such as histamine. 2. The concentration of IL-1beta in mesenteric lymph and portal venous plasma in anaesthetized cats was measured with an enzyme-linked immunosorbent assay before, during and after 10 min of abdominal ischaemia. The level of IL-1beta was significantly increased during ischaemia in lymph, but not in plasma. 3. Discharge activity of single-unit abdominal visceral C fibre afferents was measured from the right thoracic sympathetic chain. Ischaemically sensitive C fibre afferents were identified according to their response to 5-10 min of abdominal ischaemia. 4. Intra-arterial (i.a.) injection of a high dose of IL-1beta (500 ng kg-1), but not of a lower dose (i.e. 15, 50 or 150 ng kg-1), stimulated most (six of seven) abdominal visceral afferents. 5. IL-1beta (15 ng kg-1, i.a.) significantly enhanced the increased activity of 11 of 13 C fibre afferents during 10 min of ischaemia. Conversely, an IL-1 type I receptor antagonist (IL-1ra, 1.5 microg kg-1, i.a.) significantly attenuated the increased activity in six of seven other C fibre afferents during ischaemia. 6. IL-1beta (15 ng kg-1, i.a.) significantly augmented the responses of 13 of 16 ischaemically sensitive abdominal afferents to histamine (5-10 microg kg-1, i.a.). Conversely, IL-1ra (1.5 microg kg-1, i.a.) significantly attenuated the responses of five of six other C fibre afferents to histamine. 7. These data strongly suggest that stimulation of IL-1 type I receptors by IL-1beta produced during brief abdominal ischaemia contributes to activation of visceral afferents during ischaemia, at least in part, by sensitizing the afferent nerve endings to ischaemia. Our data also show that exogenous IL-1beta sensitizes visceral afferents to histamine.

Circumvention of tumor multidrug resistance by a new annonaceous acetogenin: atemoyacin-B.

AIM: To explore the effect of atemoyacin-B (Ate) on overcoming multidrug resistance (MDR). METHODS: Bullatacin (Bul) was used as a positive control. Cytotoxic effects of Bul and Ate were studied with cell culture of human MDR breast adenocarcinoma cells, MCF-7/Dox and human KBv200 cells, and their parental sensitive cell lines MCF-7 and KB. Cytotoxicity was determined by tetrazolium (MTT) assay. The function of P-glycoprotein (P-gp) was examined by Fura 2-AM assay. Cellular accumulation of doxorubicin (Dox) was determined by fluorescence spectrophotometry. Apoptosis was measured by flow cytometry. RESULTS: IC50 of Ate for MCF-7/Dox, MCF-7, KBv200, and KB cells were 122, 120, 1.34, and 1.27 nmol.L-1, respectively. IC50 of Bul for MCF-7/Dox, MCF-7, KBv200, and KB cells were 0.60, 0.59, 0.04, and 0.04 nmol.L-1, respectively. The cytotoxicities of Bul and Ate to MDR cells were similar to those to parental sensitive cells. Bul and Ate markedly increased cellular Fura-2 and Dox accumulation in MCF-7/Dox cells, but not in MCF-7 cells. The rates of apoptosis in MDR cells were similar to those in sensitive cells induced by Ate. CONCLUSION: There was no cross-resistance of P-gp positive MCF-7/Dox and KBv200 cell lines to Bul and Ate as compared with their sensitive P-gp negative MCF-7 and KB cell lines. The mechanism of the circumvention of MDR was associated with the decrease of P-gp function and the increase of cellular drug accumulation in MDR cells.

Reflex pressor response to arterial phenylbiguanide: role of abdominal sympathetic visceral afferents.

Phenylbiguanide (PBG), a 5-HT3 (serotonin) receptor agonist, has been used in many studies as a "selective" agonist to elicit reflex bradycardia and hypotension through activation of cardiac and pulmonary vagal afferents. Because we have shown that endogenous 5-HT stimulates ischemically sensitive abdominal sympathetic afferents through 5-HT3 receptors, we investigated the possibility that left ventricular (LV) and intra-arterial administration of PBG may evoke a competing reflex response by increasing the activity of sympathetic visceral afferents in anesthetized cats. Mean arterial pressure (MAP) and heart rate (HR) were monitored. When both vagal and sympathetic afferents were intact, PBG (40 microgram/kg, injected into the LV) significantly decreased MAP and HR in 8 of 10 cats but increased MAP in the remaining 2 cats. After bilateral cervical vagotomy, LV PBG significantly increased MAP. PBG (40 microgram/kg ia) significantly increased MAP and HR, whereas intravenous PBG significantly decreased MAP and HR (n = 10 cats). Furthermore, the pressor response to PBG (40 microgram /kg ia) was reduced by 68% (P < 0.05; n = 4 cats) by celiac and mesenteric ganglionectomies. In studies of single-unit abdominal sympathetic afferents, intra-arterial but not intravenous PBG (40 microgram/kg) significantly increased activity of 10 ischemically sensitive afferents but not ischemically insensitive afferents. Blockade of 5-HT3 receptors with tropisetron (200 microgram/kg iv) eliminated the response of the afferents and the pressor response to PBG. These data indicate that PBG administered into the LV usually, but not always, evokes a depressor response that is converted to a pressor response following cervical vagotomy. Also, intra-arterial PBG induces a pressor response by stimulating 5-HT3 receptors largely associated with ischemically sensitive abdominal sympathetic afferents.

Clinical aspects of the hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) can be clinically classified into two types: typical cases with a diarrheal prodrome of association with E. coli O157, and atypical cases without antecedent diarrhea. However, HUS is not common in Taiwan. To evaluate the clinical course, complications and outcome of HUS in children, and to identify the risk factors for mortality, retrospectively, seven cases of HUS in our hospital in the past 6 years were studied. Six of them were boys, and one was a girl. Their ages ranged from 0.67 to 3 years. None of them were preceded by diarrheal prodrome. Acute renal failure, hypertension and liver involvement were noted in all cases. Stroke and seizure developed in three of the cases with sequelae. Two cases progressed into end-stage renal disease (ESRD). One case developed acute respiratory distress syndrome (ARDS). Two cases (28.5%) expired. ESRD especially associated with ARDS was highly related to mortality.

Signal transduction in activation of ischemically sensitive abdominal visceral afferents: role of PKC.

Abdominal ischemia reflexly activates the cardiovascular system by stimulating abdominal visceral afferent nerve endings. Whereas many ischemic metabolites responsible for activating these nerves have been identified (e.g., bradykinin), their precise mechanism of action is unclear. Protein kinase C (PKC) is an important part of the signal transduction process underlying the action of metabolites such as bradykinin and is a regulator of neuronal activity. Therefore, we hypothesized that PKC contributes to stimulation of ischemically sensitive abdominal visceral afferents. Single-unit activity was recorded from the right thoracic sympathetic chain of anesthetized cats. Exogenous activation of PKC using phorbol 12, 13-dibutyrate (PDBu, 5 microg/kg ia) increased the impulse activity of ischemically sensitive C-fiber afferents from 0.04 +/- 0.01 to 0. 67 +/- 0.23 impulses/s (n = 11; P < 0.05). The influence of endogenous activation of PKC also was evaluated during 10 min of mesenteric ischemia. Inhibition of PKC using PKC-(19-36) (20 microg/kg iv) reduced ischemia-induced increases in afferent activity from 0.46 +/- 0.11 to 0.19 +/- 0.08 impulses/s (n = 7, P < 0.05). Moreover, PKC-(19-36) (20 microg/kg iv) reduced the response of ischemically sensitive C fibers to bradykinin (0.5-1.0 microg/kg ia) from 1.18 +/- 0.20 to 0.66 +/- 0.14 impulses/s (n = 13, P < 0. 05). These results indicate that PKC contributes to activation of abdominal visceral afferents during ischemia and specifically to part of the bradykinin-induced activation of these afferents.

Clinical efficacy of cyclosporin a neoral in the treatment of paediatric lupus nephritis with heavy proteinuria.

Cyclosporin A (CsA) was introduced in recent years for the treatment of lupus nephritis in patients with steroid resistance or in those with severe corticosteroid toxicity. Our previous study on paediatric patients showed that Neoral (a new microemulsion formulation) had better bioavailability than CsA capsules. To evaluate the clinical efficacy of Neoral in children with lupus nephritis compared with conventional therapy, we performed an open randomized study on 40 children, ranging from 9 to 14 yr old, with class III-V lupus nephritis and heavy proteinuria. They were randomly assigned to either Neoral (5 mg/kg/day), administered q.12.h, or prednisolone (2 mg/kg/day) plus cyclophosphamide (2 mg/kg/day) for 1 yr. Both groups showed a significant decrease in proteinuria (Neoral: 4.62 +/- 1.93 to 0.35 +/- 0.29 g/day, P < 0.05; prednisolone plus cyclophosphamide: 4.52 +/- 1.86 to 0.62 +/- 0.21 g/day, P < 0.01). The CH50 haemolytic assay titre decreased after 1 yr of Neoral treatment (26.5 +/- 0.9 to 21.4 +/- 2.2 U/ml, P < 0.05). Serum C3 and anti-double-stranded (ds) DNA antibody levels also fell with Neoral (C3: 86.2 +/- 6.8 to 76.3 +/- 4.5 mg/dl; anti-ds DNA antibodies: 14.1 +/- 3.2 to 8.2 +/- 1.4 IU/ml, P < 0.05). The Neoral group had a significant increase in growth rate over the prednisolone plus cyclophosphamide group (8.2 +/- 1.1 cm/yr vs 2.7 +/- 0.6 cm/yr, P < 0.01) with improvement of growth status. During the study period, patients tolerated Neoral well with no significant changes in renal function, liver function or lipid profile. Our study implies that Neoral appears to be effective in suppressing proteinuria. Neoral should be regarded as being adjunctive therapy, perhaps with a steroid-sparing effect, in paediatric lupus nephritis. However, its long-term use awaits further studies.

Role of 5-HT3 receptors in activation of abdominal sympathetic C fibre afferents during ischaemia in cats.

1. Activation of abdominal sympathetic afferents during ischaemia reflexly excites the cardiovascular system. We have shown previously that exogenous 5-hydroxytryptamine (5-HT, i.e. serotonin) stimulates abdominal sympathetic afferent nerve endings, and recently have documented increased concentrations of 5-HT in intestinal lymph and portal venous plasma during brief abdominal ischaemia. The present investigation evaluated the role of endogenously produced 5-HT in activation of ischaemically sensitive abdominal sympathetic afferents. 2. Nerve activity of single-unit C fibre afferents innervating duodenum, mesentery, pancreas, portal hepatis, bile duct, gall bladder and jejunum was recorded from the right thoracic sympathetic chain of anaesthetized cats. Ischaemically sensitive C fibre afferents were identified according to their response to 5-10 min of abdominal ischaemia. 3. Intra-arterial injection of 5-HT (20 microg kg-1) increased discharge activity of twelve afferents from 0. 23 +/- 0.05 to 0.96 +/- 0.09 impulses s-1 after an onset latency of 5.7 +/- 1.4 s. Also, 2-methylserotonin (100 microg kg-1, i.a.), a 5-HT3 receptor agonist, stimulated eleven of twelve afferents to significantly increase their discharge activity from 0.25 +/- 0.05 to 0.90 +/- 0.10 impulses s-1 after a latency of 3.3 +/- 0.4 s. Furthermore, intravenous injection of tropisetron (200 microg kg-1), a 5-HT3 receptor antagonist, significantly attenuated the increase in activity of twelve other C fibre afferents during 10 min of abdominal ischaemia from 1.62 +/- 0.18 to 0.94 +/- 0.22 impulses s-1, and eliminated the response of eleven other afferents to 5-HT. 4. Both the 5-HT2 receptor agonist, alpha-methylserotonin (100 microg kg-1, i.a.), and the 5-HT1 receptor agonist, 5-carboxamidotryptamine (100 microg kg-1, i.a.), did not alter the impulse activity of these twelve afferents (0.29 +/- 0.05 to 0.31 +/- 0.06, and 0.26 +/- 0.06 to 0.29 +/- 0.06 impulses s-1, respectively). 5. Treatment with indomethacin (5 mg kg-1, i.v.) in eight different cats did not alter the response of nine C fibre afferents to exogenous 5-HT (0.91 +/- 0. 17 vs. 1.19 +/- 0.25 impulses s-1, P > 0.05). 6. The results suggest that, during mesenteric ischaemia, endogenous 5-HT contributes to the activation of abdominal sympathetic afferents, mainly through direct stimulation of 5-HT3 receptors and that the action of 5-HT on these afferents appears to be independent of the cyclo-oxygenase pathway.

IgG subclass/IgM ratio and response to therapy in focal segmental glomerulonecrosis.

Focal segmental glomerulosclerosis (FSGS) is relatively steroid resistant and no clinical or histological marker can predict the response to therapy. To investigate the role of serum immunoglobulin subclass/IgM in predicting the response to therapy in FSGS, serum concentrations of total IgG, IgG subclasses, and the ratio of serum IgG subclasses to total IgG (% IgG subclass) were measured in 27 children during the acute nephrotic state. Prednisolone, cyclophosphamide, and Persantine (dipyridamole) were given for 12 weeks. We divided the patients into good responders or poor responders according to clinical response. The clinical and nephrotic status were similar in both groups. Fourteen patients were good responders with higher serum IgGI/IgM than that of non-responders (4.00+/-0.67 vs. 1.61+/-0.20, P<0.05). There was no significant difference in IgG2/IgM between these two groups. These results suggest that higher serum IgGI/IgM ratios may be associated with a better clinical response. These changes may reflect dysregulation of immunoglobulin class switching in patients with FSGS.

Formalin treatment of refractory hemorrhagic cystitis in systemic lupus erythematosus.

Hemorrhagic cystitis is a potentially life-threatening complication in systemic lupus erythematosus (SLE). No safe, effective and conservative treatment exists for patients who fail to respond to standard therapy. We report a 17-year-old girl with SLE who suffered from severe hemorrhagic cystitis. Initially, she received frequent red blood cell and platelet transfusions, continuous bladder irrigation, and blood clots were evacuated. Numerous kinds of treatment were tried, including electrocoagulation of bleeding foci, prostaglandin E1 bladder instillation, and hyperbaric oxygen. However, she remained severely anemic and thrombocytopenic necessitating daily transfusions of blood products. After intravesical formalin instillation was performed twice, the hematuria ceased completely.

Reversal of tumor multidrug resistance by 2-phenyl-3-(3',5'-dimorpholinomethyl-4'-hydroxy)-benzoyl-indole (HWL-12).

AIM: To explore the reversal of multidrug resistance (MDR) by indole derivative HWL-12. METHODS: Cytotoxicity was determined by tetrazolium (MTT) assay. The function of P-gp was examined by Fura 2-AM assay. Cellular accumulation of doxorubicin (Dox) was measured by fluorescence spectrophotometry. RESULTS: HWL-12 10 mumol.L-1 markedly increased Fura-2 accumulation and was 17.2-fold reversal of MDR in MCF-7/ADR cells. The cellular Dox accumulation in MDR cells was increased in the presence of HWL-12 on the MCF-7/ADR cells. No effect was observed for Dox accumulation in the presence of high Ca2+ (addition of CaCl2) or low Ca2+ (addition of egtazic acid). CONCLUSION: HWL-12 has a potent MDR reversal action which was associated with the increase of cellular Dox accumulation in MDR cells and not related with calcium ion concentration.