Allicin Improves Cardiac Function by Protecting against Apoptosis in Rat Model of Myocardial Infarction

Objective:To study the effects of allicin on cardiac function and underlying mechanism in rat model of myocardial infarction(MI).Methods:Ninety-four Wistar rats were randomly assigned to 6 groups(n=14–16 per group):sham control group[underwent thoracotomy without left anterior descending(LAD)occlusion and only received an injection of the same amount of citrate buffer],MI control group(subjected to LAD occlusion and only received an injection of same amount of citrate buffer),positive control group(subjected to LAD occlusion and received an injection of diltiazem hydrochloride at the dose of 1.5 mg/kg),and MI+allicin groups(subjected to LAD occlusion and received an injection of allicin at the doses of 1.2,1.8,and 3.6 mg/kg).All of the drugs were administered intraperitoneally daily for 21 days.The infarct area was measured by myocardial staining.Hematoxylin-eosin staining was used to observe the pathological changes.Cardiac function parameters were assessed by echocardiography.The myocardial apoptotic index was estimated by terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling staining.The expression of Bax and Bcl-2 were detected by quantificational real-time polymerase chain reaction and Western blot.Results:Treatment with allicin could attenuate the myocardial infarct area(P0.05)and relieve the changes of the myocardium.The left ventricular anterior wall diastolic and systolic thicknesses were increased in the allicin-treated groups(P0.05),while there was no significant difference in the left ventricular posterior wall diastolic and systolic thickness(P0.05).The left ventricular internal diameter in systole,ejection fraction,fractional shortening,and stroke volume were dramatically elevated in allicin-treated rats(P0.05).Allicin dose-dependently reduced creatine kinase and lactate dehydrogenase levels(P0.05).The myocardial apoptotic index was also markedly lowered,and Bax expression was significantly decreased,whereas Bcl-2 expression exhibited an opposite trend in allicin-treated rats(P0.05).Conclusion:Allicin appears to exert a cardioprotective effect that may be linked to blocking Bcl-2/Bax signaling pathway-denpendent apoptosis,further improving cardiac function.     

Prophylactic Herbal Therapy Prevents Experimental Ascending Urinary Tract Infection in Mice

Objective

To study the preventive effect of herbal formulation on experimental murine urinary tract infection (UTI) induced by Dr Escherichia coli 11128.

Methods

E. coli 11128 carrying Dr fimbriae was isolated from patients with chronic pyelonephritis. The minimal inhibitory concentration (MIC) value of herbal solution for E. coli 11128 was determined for further studies. Forty C3H/HeJ mice were divided into the herb-treated group (n=20, given Chinese herbs by gavage at an average dose of 20 g/kg body weight daily 3 days before inoculation), and control group (n=20, given the same amount of distilled water by gavage). Three and 6 days after infection, bacteria were counted in the urine and the kidneys of the mice. Kidney histopathologic changes were evaluated. Neutrophils infiltration and accumulation were detected.

Results

The MIC value of herbal solution was 0.1 g/mL for the E. coli 11128. In herb-treated mice, there was a significant reduction in bacterial counts in urine and colonization densities of kidneys. Microscopic studies revealed signs of inflammation in kidneys. In herb-treated mice, herbal administration resulted in significantly reduced neutrophilic infiltrates (P<0.05). The semi-quantitative scores for renal lesions were significantly lower (P<0.05).

Conclusion

Prophylactic administration of herbal formulation potentiated the effect in partially preventing experimental murine ascending UTI.

     

Acute and Sub-chronic Toxicity of Tetrandrine in Intravenously Exposed Female BALB/c Mice

Objective: To evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine(TET) in female BALB/c mice. Methods: The median lethal dose(LD_(50)) of intravenously administered TET was calculated in mice using Dixon's up-and-down method. In the acute toxicity study, mice were intravenously administered with TET at a single dose of 20, 100, 180, 260 and 340 mg/kg, respectively and were evaluated at 14 days after administration. In the sub-acute toxicity study, mice were intravenously administered various doses of TET(30, 90 and 150 mg/kg) each day for 14 consecutive days. Clinical symptoms, mortality, body weight, serum biochemistry, organ weight and histopathology were examined at the end of the experiment, as well as after a 1-week recovery period. Result: LD_(50) was found to be 444.67±35.76 mg/kg. In the acute toxicity study, no statistically significant differences in body weight, blood biochemistry, or organ histology were observed between the administration and control groups when mice were intravenously administered with single dose at 20, 100, 180, 260 and 340 mg/kg of TET(P0.05). In the sub-acute toxicity study, no significant changes in body weight, biochemistry and organ histology were observed with up to 90 mg/kg of TET compared with the control group(P0.05), however, in the 150 mg/kg administered group, TET induced transient toxicity to liver, lungs and kidneys, but withdrawal of TET can lead to reversal of the pathological conditions. Conclusions: The overall findings of this study indicate that TET is relatively non-toxic from a single dose of 20, 100, 180, 260 or 340 mg/kg, and that up to 90 mg/kg daily for 14 consecutive days can be considered a safe application dose.     

Ethanol Extract of Ilex Hainanensis Merr. Exhibits Anti-Melanoma Activity by Induction of G1/S Cell-Cycle Arrest and Apoptosis

Objective: To evaluate anti-melanoma effect of ethanol extract of Ilex hainanensis Merr. (IME) and elucidate its underlying mechanism. Methods: Thirty-six tumor-bearing mice were randomized into 6 groups (n=6) as follows: model group, IME 25, 50, 100, and 200 mg/kg groups and dacarbazine (DTIC) 70 mg/kg group. The mice in the IME treatment groups were intragastrically administered with IME 25, 50, 100 or 200 mg/kg per day, respectively. The mice in the DTIC group were intraperitoneally injected with DTIC 70 mg/kg every 2 days. The drug administration was lasting for 14 days. The cell viability was evaluated by 3-(4,5-dime-thylthylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Flow cytometry was employed to detect cell cycle and apoptosis. The gene and protein expressions of nuclear factor κB-p65 (NF-κB-p65), Bcl-2, B-cell lymphoma-extra large (Bcl-xL) and Bax were detected by quantitative real-time polymerase chain reaction and Western blot analyses. Caspases-3, -8, and -9 activities were detected using the colorimetric method. In addition, a B16-F10 melanoma xenograft mouse model was used to evaluate the anti-cancer activity of IME in vivo. Furthermore, a survival experiment of tumor-bearing mice was also performed to evaluate the possible toxicity of IME. Results: IME significantly inhibited the proliferation of B16-F10 cells (P<0.01). Flow cytometric analysis showed that IME induced G1/S cell cycle arrest and apoptosis (both P<0.01). IME inhibited activation of NF-κB, decreased the gene and protein expressions of Bcl-2, Bcl-xL, and increased the gene and protein expressions of Bax (all P<0.01). In addition, IME induced the activation of Caspases-3, -8, and -9 in B16-F10 cells. The study in vivo showed that IME significantly reduced tumor volume (P<0.01), and the inhibitory rate came up to 68.62%. IME also induced large areas of necrosis and intra-tumoral apoptosis that correlated with a reduction in tumor volume. Survival experiment showed that treatment with IME for 14 days significantly prolonged survival time and 20% of mice in the IME 200 mg/kg group were still alive until the 50th day. Notably, IME showed no apparent side-effects during the treatment period. Conclusion: IME exhibited significant anti-melanoma activity in vitro and in vivo, suggesting that IME might be a promising effective candidate with lower toxic for malignant melanoma therapy.     

Determination of intrarenal resistance index (RI) in patients with multiple myeloma

Background

Renal impairment is a common complication of multiple myeloma occuring in up to 50% of patients at some stage in their disease. Due to occurrence of cast nephropathies we hypothesized circulatory dysregulation (vasoconstriction) in the kidneys with measurable elevation of the resistance index among these patients which would have a diagnostic impact.

Subjects and methods

36 patients with treated multiple myeloma (21 females, 15 males, mean age 61.6 ± 8.5 years) were prospectively examined by conventional abdominal ultrasound with focussed investigation of the kidneys. First, length of the organs, parenchymal width and characterization of parenchymal echogenicity were determined. Then, intrarenal RI values were measured in segmental and arcuate arteries, respectively, in both kidneys. Additionally, serum creatinine, BUN and GFR of each patient were evaluated. RI values were compared to values of 78 healthy control subjects.

Results

Mean renal RI was 0.68 ± 0.07 which was slightly higher than in controls with 0.62 ± 0.05, but without statistical significance. Due to the laboratory analyses patients were subdivided in those with normal (group 1, n = 21) and those with impaired (group 2, n = 15) renal function. In both groups kidney size and parenchymal width were normal. Significant more group 2 patients (60%) revealed hyperechogenic par enchyma than group 1 patients (24%) (p < 0.01). Mean renal RI indices were 0.67 ± 0.06 (right) and 0.69 ± 0.06 (left) in group 1 patients and 0.71 ± 0.08 (right) and 0.71 ± 0.07 (left) in group 2 patients and showed no significant difference (p = 0.06 and 0.15).

Conclusion

Renal RI values are not significantly elevated in patients with multiple myeloma even in those with renal impairment so that no hints to a relevant vasoconstriction could be evaluated. RI seems not to be a relevant parameter for the diagnosis of cast nephro pathy of multiple myeloma patients. Routinely performed ultrasound examination should be more focussed on the qualification of parenchymal echogenicity.

     

Wet Cupping Therapy Improves Local Blood Perfusion and Analgesic Effects in Patients with Nerve-Root Type Cervical Spondylosis

Objective

To observe wet cupping therapy (WCT) on local blood perfusion and analgesic effects in patients with nerve-root type cervical spondylosis (NT-CS).

Methods

Fifty-seven NT-CS patients were randomly divided into WCT group and Jiaji acupoint-acupuncture (JA) group according a random number table. WCT group (30 cases) was treated with WCT for 10 min, and JA group (27 cases) was treated with acupuncture for 10 min. The treatment efficacies were evaluated with a Visual Analogue Scale (VAS). Blood perfusion at Dazhui (GV 14) and Jianjing (GB 21) acupoints (affected side) was observed with a laser speckle flowmetry, and its variations before and after treatment in both groups were compared as well.

Results

In both groups, the VAS scores significantly decreased after the intervention (P<0.01), while the blood perfusion at the two acupoints significantly increased after intervention (P<0.05); however, the increasement magnitude caused by WCT was obvious compared with JA (P<0.05).

Conclusions

WCT could improve analgesic effects in patients with NT-CS, which might be related to increasing local blood perfusion of acupunct points.

     

Multi-drug Resistant Uropathogenic Escherichia coli and Its Treatment by Chinese Medicine

Objectives: To investigate the resistance and virulence profiles of uropathogenic Escherichia coli (UPEC) and its treatment by Chinese medicine (CM) Fuzheng Qingre Lishi Formula (扶正清热利湿方, FQLF). Methods: UPEC strains were isolated from recurrent urinary tract infections (UTIs) patients. Patient sensitivities to 17 antibiotics were tested by the disk diffusion method. Virulence genes were screened by plolymerase chain reaction. A mouse model was constructed using a multi-drug resistant and virulent UPEC strain and treated with FQLF or the antibiotic imipenem. The treatment efficacy was evaluated by bacterial clearance from urine and the urinary organs. Results: A total of 90 UPEC strains were collected, and 94.4% of the isolates were resistant to at least 1 antibiotic. Approximately 66.7% of the UPEC strains were multi-drug resistant. More than one virulence gene was found in 85.6% of the isolates. The extended-spectrum β-lactamases (ESBL)-positive strains were more resistant than the negative ones. The virulence gene number was positively correlated with the resistance number (P<0.05). A mouse model was successfully constructed using UPEC10. Treatment with either FQLF or antibiotics significantly cleared bacteria from the mouse urine after 14 days. In the untreated control, the bacteria lasted for 28 days. FQLF treatment of the UTI mouse model greatly reduced the bacterial number in the kidney and bladder, but could not completely clear the bacteria. Conclusions: Multi-drug resistance is common among UPEC isolates, and the resistance is positively related with virulence. FQLF could treat UPEC UTIs, but could not completely clear the bacteria from the host.     

Acupuncture Points Used in the Prophylaxis against Recurrent Uncomplicated Cystitis, Patterns Identified and Their Possible Relationship to Physiological Measurements

Objective

To explore the correlation between single acupoints used and the recurrence rate of cystitis among cystitis-prone women receiving acupuncture as a prophylactic treatment.

Methods

In all, 58 cystitis-prone women were included in the analysis. Customised acupuncture treatments were given twice a week, over 4 weeks. The main effect parameter was the number of cystitis episodes during the 6-month observation time. Residual urine was measured at baseline, 2, 4 and 6 months using portable ultrasound equipment. Sympathetic and vagotone nerve activities were measured by using skin conductance and respiratory sinus arrhythmia, respectively.

Results

The main acupoints used for patients with Kidney (Shen) qi/yang deficiency were Shenshu (BL23), Taixi (KI3), Zhongji (CV3), Sanyinjiao (SP6) and Pangguangshu (BL28), compared with Taichong (LR3), CV3, BL28, Yinlingquan (SP9) and SP6 for Liver (Gan) qi stagnation, and SP6, CV3, BL28, Zusanli (ST36) and SP9 for Spleen (Pi) qi/yang deficiency patients. The combination BL23 and KI3 were used in 16 women, 13 of which were Kidney pattern related patients. When used, the number of symptomatic episodes were reduced to a third compared with what occurred in the 42 women where this combination was not used (3/16 vs. 28/42, P<0.05). BL23 application correlated to a significant reduction in residual urine measured a few days after treatment. Patients with the pattern of Spleen qi/yang deficiency had an initial increase in residual urine after treatments.

Conclusion

Treating Kidney pattern related patients with the combination of BL23 and KI3 resulted in far better outcome than other points/combination of points for other Chinese medicine diagnoses. The acupoint SP6 may be less indicated than previously assumed when treating cystitis-prone women prophylactically.

     

Changes in Small Intestinal Motility and Related Hormones by Acupuncture Stimulation at Zusanli (ST 36) in Mice

Objectives

To clarify the effects of acupuncture stimulation at Zusanli (ST 36) on the hormonal changes.

Methods

Eight-week-old male C57BL/6 mice received acupuncture stimulation at acupoint ST 36 or Quchi (LI 11) once a day for 3 or 5 days in the acupuncture-stimulated groups, but not received in the normal group (n=6 in each group). On day 3 or 5, animals were given 0.1 mL of charcoal orally with a bulbed steel needle, 30 min after the last acupuncture stimulation. Ten minutes later, mice were anesthetized, and the intestinal transit and the concentrations of vasoactive intestinal peptide (VIP), motilin, ghrelin and gastrin in the serum were measured.

Results

Compared to no acupuncture stimulation, acupuncture stimulation at ST 36 for 5 days increased the intestinal transit and down-regulated the concentration of VIP and up-regulated the concentrations of motilin, ghrelin and gastrin (P<0.05 or 0.01), whereas acupuncture stimulation at LI 11 did not change them signifificantly (P>0.05).

Conclusion

Acupuncture stimulation at ST 36 for 5 days enhances the small intestinal motility and regulates the secretion of hormones related to small intestinal motility.

     

Chinese Tuina Downregulates the Elevated Levels of Tissue Plasminogen Activator in Sciatic Nerve Injured Sprague-Dawley Rats

Objective

To elucidate the mechanism of Chinese tuina in treating sciatic nerve crush injury, and to detect the levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), which is thought to play an important role in nerve regeneration.

Methods

Thirty-two adult male Sprague-Dawley rats were subjected to sciatic nerve crush injury and 16 rats (sham-operated group) went through a sham operation. Control group was given no treatment while tuina group received tuina therapy since day 7 post-surgery. Tuina treatment was performed once a day and lasted for 20 days. The sciatic functional index was examined every 5 days during the treatment session. The rats’ gastrocnemius muscles were evaluated for changes in mass and immunohistochemistry techniques were performed to detect the levels of tPA and PAI-1.

Results

Tuina therapy improved the motor function of sciatic nerve injured rats (P<0.05), however, it did not increase muscle volume (P<0.05). Tuina downregulated the levels of tPA and PAI-1 (P<0.05).

Conclusions

The present study implies that tuina treatment could accelerate rehabilitation of peripheral nerve injury.

     

Xuezhikang(血脂康) Reduced Renal Cell Apoptosis in Streptozocin-Induced Diabetic Rats through Regulation of Bcl-2 Family

Objective: To investigate the effect of Xuezhikang(血脂康, XZK) on renal cell apoptosis in diabetic rats and the possible mechanism. Methods: Sixty-six rats were randomly divided into 3 groups: the normal, model and XZK groups. In each group, the rats were further randomly divided into 3-month and 6-month subgroups, respectively. Diabetes of rats was induced by a single intraperitoneal injection of 1% streptozocin at 60 mg/kg body weight. Rats in the XZK group received gastric perfusion of XZK(1200 mg/kg body weight) everyday for 3 or 6 months, while rats in the normal and model groups received equal volume of saline. Twenty-four hours' urine was collected for urinary albumin excretion(UAE) measurement. Periodic acid-Schiff(PAS) and Masson's trichrome staining were used for saccharides and collagen detection. Cell apoptosis of renal cortex was investigated by Td T-mediated d UTP nick end labeling(TUNEL) staining. Bax and Bcl-2 expressions were detected by immunohistochemistry and Western blot, respectively. Cytochrome C(Cyt C) and caspase-9 concentration were detected by Western blot. Results: Compared with the model group, XZK treatment could significantly decrease the kidney hypertrophy index, 24 h UAE, renal cell apoptosis, cytoplasmic Cyt C level and active caspase-9 level, as well as suppress the increment of Bax and up-regulate the expression of Bcl-2, leading to the suppression of Bax/Bcl-2 ratio at 3 and 6 months(P0.05 or P0.01). Moreover, XZK treatment could alleviate the deposition of PAS-stained saccharides and Masson's trichromestained collagen to different extent. Conclusions: Renal cell apoptosis was observed in diabetic kidney, in which mitochondrial apoptotic pathway might be involved. XZK treatment could attenuate pathological changes in diabetic kidney and reduce renal cell apoptosis, probably via the suppression of Bax/Bcl-2 ratio, which lead to inhibition of Cyt C release and following caspase-9 activation.     

An Ethical Evaluation Index System for Clinical Approval of Medical Technology in China: A Structural Equation Model Study

Objective

To construct a quantitative ethical evaluation index system for the clinical approval of medical technology in China.

Methods

Exploratory factor analysis (EFA) and first-order confirmatory factor analysis (CFA) based on a structure equation model (SEM), higher-order CFA and normalisation were used to establish an ethical evaluation index system for the clinical approval of medical technology. Data were processed in SPSS 13.0 and Lisre l5.3.

Results

There were 52 third class indices, 15 second class indices, and 3 first class indices in this ethical evaluation index system. The weight of each index was calculated by normalisation.

Conclusion

This study developed a three-level ethical evaluation index system, comprising 70 indices, for the clinical approval of medical technology.

     

Transbronchial catheter aspiration compared to forceps biopsy in the diagnosis of peripheral lung cancer

Objective

The usual procedure for obtaining material for histological analysis for the diagnosis of peripheral carcinoma of the lung is transbronchial forceps biopsy (TBB). Not widely spread is acquiring samples for cytological examination by transbronchial catheter aspiration (TBCA). Data were retrospectively collected to determine the diagnostic sensitivity of TBCA in comparison with TBB concerning malignancy.

Methods

We analysed the results of 51 consecutively examined patients (age 68.7 ± 8.8 yrs.) applying both methods. 48 of 51 peripheral lesions proved to be malignant, 34 of which measured > 3 cm in diameter and 14 ≤ 3 cm. Fluoroscopy provided guidance in biopsies for both techniques.

Results

The mean diameter of the lesion was 3.7 ± 1.5 cm. We were able to establish a correct diagnosis by TBCA in 36 of 48 patients with lung cancer, and in 21 of 48 patients by TBB (75% vs. 44%, p < 0.01, chi-square-test). By combination of both methods 39 of 48 patients were correctly diagnosed. For carcinoma > 3 cm the success rate for TBCA was 76% (26/34) and for TBB 56% (19/34). For carcinoma ≤ 3 cm the success rate for TBCA was 71% (10/14) and for TBB 14% (2/14).

Conclusions

Even in lesions ≤ 3 cm application of TBCA results in an only marginally lower success rate compared to lesions > 3 cm. Due to the overall high success rate we suggest to apply the easy-to-handle and inexpensive method of TBCA in diagnostic procedure of peripheral lung carcinoma.

     

Icariin Improves Cognitive Impairment after Traumatic Brain Injury by Enhancing Hippocampal Acetylation

Objective

To examine the effect of icariin (ICA) on the cognitive impairment induced by traumatic brain injury (TBI) in mice and the underlying mechanisms related to changes in hippocampal acetylation level.

Methods

The modifified free-fall method was used to establish the TBI mouse model. Mice with post-TBI cognitive impairment were randomly divided into 3 groups using the randomised block method (n=7): TBI (vehicle-treated), low-dose (75 mg/kg) and high-dose (150 mg/kg) of ICA groups. An additional sham-operated group (vehicle-treated) was employed. The vehicle or ICA was administrated by gavage for 28 consecutive days. The Morris water maze (MWM) test was conducted. Acetylcholine (ACh) content, mRNA and protein levels of choline acetyltransferase (ChAT), and protein levels of acetylated H3 (Ac-H3) and Ac-H4 were detected in the hippocampus.

Results

Compared with the sham-operated group, the MWM performance, hippocampal ACh content, mRNA and protein levels of ChAT, and protein levels of Ac-H3 and Ac-H4 were signifificantly decreased in the TBI group (P<0.05). High-dose of ICA signifificantly ameliorated the TBI-induced weak MWM performance, increased hippocampal ACh content, and mRNA and protein levels of ChAT, as well as Ac-H3 protein level compared with the TBI group (P<0.05).

Conclusion

ICA improved post-TBI cognitive impairment in mice by enhancing hippocampal acetylation, which improved hippocampal cholinergic function and ultimately improved cognition.

     

Pretreatment of Shaoyao Gancao Decoction (芍药甘草汤) Alters Pharmacokinetics of Intravenous Paclitaxel in Rats

Objective:To investigate the effect of Shaoyao Gancao Decoction(芍药甘草汤,SGD) on the pharmacokinetics of intravenously administered paclitaxel in rats.Methods:Paclitaxel was intravenously administered to rats(3 mg/kg) with or without the concomitant administration of SGD(752 mg/kg,a single day or 14 consecutive days pretreatment).The paclitaxel in the serum was quantified using a simple and rapid ultra performance liquid chromatography(UPLC) method for the pharmacokinetic study.The pharmacokinetic parameters were calculated via a non-compartment model using the computer program DAS 2.0.Results:The pharmacokinetic parameters of paclitaxel were significantly altered in response to 14 consecutive days of pretreatment with SGD.The area under the curve(AUC_(0-t),from 4 820 ± 197 to 4 205 ± 186 ng·mL~(-1)·h~(-1))and AUC_(0-∞)(from 5 237 ±280 to 4 514 ± 210 ng·mL~(-1)·h~(-1)) significantly decreased in response to the 14-day pretreatment with SGD.The values of V_(dss)(L/kg) were 10.74 ±1.08 and 9.35 ±0.49,those of CL(L/kg) were0.67 ±0.03 and 0.57 ±0.03 and the t_(1/2)(h) values were 11.17 ±0.84 and 11.32 ±0.93,respectively,for the14-day SGD pretreatment and intravenous paclitaxel alone.The AUC_(0-t) and AUC_(0-∞) values decreased by13%and 14%(P0.01),respectively.The area under the curve decreased significantly(P0.01),and the total clearance increased by 1.2-fold(P0.01),after 14 consecutive days of pretreatment with SGD.A single-day pretreatment with SGD did not significantly affect the pharmacokinetic parameters of paclitaxel.Conclusions:SGD administration for 14 consecutive days increased the metabolism of paclitaxel,while a 1-day pretreatment had little effect.The results would contribute important information to the study on interaction between Chinese medicines and chemotherapy and also help to utilize SGD better in the adjunctive therapy of cancer patients.     

Unravelling the genome: a review of molecular genetic research in schizophrenia

Background

Schizophrenia is a common and complex mental illness that affects approximately 1% of the population worldwide. Despite intensive research over the years, the aetiology and pathogenesis of schizophrenia is poorly understood. However, it has long been recognised that schizophrenia is highly familial suggesting a possible genetic aetiology.

Aim

To review recent molecular genetic research in schizophrenia.

Methods

Medline and Embase search.

Results

Over the past decade, with the completion of the Human Genome Project, molecular genetic research has now identified a number of genes that are very likely to predispose to schizophrenia.

Conclusion

This article discusses the methodologies that have been used to identify schizophrenia susceptibility genes and provides a review of recently identified genes thought to play a role in the pathogenesis of this illness.

     

Three generations of matrilineal excess of birth defects in Irish families with neural tube defects

Background

Neural tube defects (NTDs) and birth defects overall are more likely to occur among maternal compared to paternal relatives in two generations (uncles/aunts and first cousins) of Irish families where an individual has been born with an NTD.

Aims

The aim of this study was to determine if the matrilineal excess persisted into the third generation.

Methods

First cousins were interviewed about their pregnancy outcomes and their offsprings’ health.

Results

Maternal first cousins once removed (FCOR) were more likely to have birth defects than paternal FCOR: 6.7 versus 3.5% (adjusted odds ratio 1.49, 95% CI 0.57, 3.89). No NTDs occurred. Folic acid supplementation significantly reduced the risk of birth defects (P = 0.04).

Conclusions

This study demonstrates an excess of birth defects among maternal relatives in three consecutive generations of NTD families, and supports the hypothesis that an underlying mechanism links distant maternal relatives in at least some NTD families.

     

Effect of Wenhua Juanbi Recipe (温化蠲痹方) on Expression of Receptor Activator of Nuclear Factor Kappa B Ligand, Osteoprotegerin, and Tumor Necrosis Factor Receptor Superfamily Member 14 in Rats with Collagen-Induced Arthritis

Objective: To study the effect of Wenhua Juanbi Recipe(温化蠲痹方, WJR) on expression of receptor activator of nuclear factor kappa B ligand(RANKL), osteoprotegerin(OPG), and tumor necrosis factor receptor superfamily member 14(TNFRSF14, also known as LIGHT) in rats with collagen-induced arthritis(CIA). Methods: CIA rats were generated by subcutaneous injection of bovine collagen type-Ⅱ at the tail base. Sixty CIA rats were randomly assigned(10 animals/group) to: model, methotrexate(MTX)-treated(0.78 mg/kg body weight), and WJR-treated(22.9 g/kg) groups. Healthy normal rats(n=10) were used as the normal control. Treatments or saline were administered once daily by oral gavage. Rats were sacrificed at day 28 post-treatment and knee synovium and peripheral blood serum were collected. Toe swelling degree and expression of RANKL, OPG, and LIGHT were determined by Western blot and immunohistochemistry. Results: Compared with the normal group, toe swelling degree was significantly increased in the model group(P0.01). After treatment, toe swelling degree decreased significantly in the WJR and MTX groups compared with the model group(P0.01). Compared with the normal group, expression of RANKL and LIGHT were significantly increased and OPG significantly decreased in peripheral blood and synovium of the model group(P0.01). Conversely, RANKL and LIGHT expression were significantly reduced and OPG increased in the WJR and MTX groups compared with the model group(P0.01). No statistically significant difference existed between WJR and MTX groups. Conclusion: WJR likely acts by reducing RANKL expression and increasing OPG expression, thus inhibiting RANKL/RANK interaction and reducing LIGHT expression, thereby inhibiting osteoclast formation/activation to block bone erosion.     

Suppression of Oxidative Stress of Modified Gongjin-Dan (WSY-1075) in Detrusor Underactivity Rat Model Bladder Outlet Induced by Obstruction

Objective

To investigate the anti-oxidative stress and preventive effect of modified Gongjin-dan (WSY-1075) in a detrusor underactivity rat model.

Methods

Rats were randomly allocated to three groups: shamoperated (control), bladder outlet obstruction-induced detrusor underactivity (BOO-DU), and BOO-DU with WSY-1075 (WSY) groups. WSY-1075 was orally administrated to rats 200 mg daily for 2 weeks prior to the operation and 4 weeks after the operation. Bladder outlet obstruction was surgically induced in rats by ligation around the urethra avoiding total obstruction. Cystometrography was conducted on rats in each group for examination of bladders.

Results

Compared with the control group, bladder outlet obstruction led to a significant increase in oxidative stress with consequent changes to molecular composition, and decrease in maximal detrusor pressure (P<0.05). WSY-1075 treatment significantly suppressed oxidative stress and prevented degenerative and dysfunctional changes in bladder, as compared with BOO-DU group (P<0.05).

Conclusion

WSY-1075 had beneficial effect on prevention of BOO-DU.

     

Haoqin Qingdan Decoction (蒿芩清胆汤) and Ribavirin Therapy Downregulate CD14 and Toll-Like Receptor 4 in Febrile Disease with Dampness-Heat Syndrome in A Mouse Model

Objective: To evaluate the effect of Chinese medicine Haoqin Qingdan Decoction(蒿芩清胆汤, HQD) for febrile disease dampness-heat syndrome(FDDHS). Methods: Forty mice were divided into four groups, including normal control, FDDHS(induced by Radix et Rhizoma Rhei recipe and influenza virus A1 FM1 model), HQD, and the ribavirin groups(10 in each). The normal control and FDDHS groups were administered normal saline. HQD and the ribavirin groups were administered HQD and ribavirin intragastrically once daily at a dose of 64 g/(kg·d) and 0.07 g/(kg·d), respectively for 7 days. Lethargy, rough hair, diarrhea, tongue color and sole color were evaluated for pathological changes in morphology. The tongue and lung tissues were collected for histology. The CD14 and toll-like receptor 4(TLR4) expression levels were measured using real-time quantitative polymerase chain reaction. Results: More than 80% of the FDDHS mice showed hypokinesia and lethargy, and pathological changes associated with rough hair, diarrhea, tongue color and sole color. With advanced treatment for 7 days, the thick greasy tongue fur of the HQD and ribavirin groups were thinner than that of the FDDHS group(P0.05), and it was the thinnest in the ribavirin group as compared with that in other groups(P0.05). The CD14 and TLR4 expression levels in the lung tissues of HQD and ribavirin groups significantly delined compared with the model group(P0.05 or P0.01). CD14 was down-regulated more remarkably in the HQD group compared with the ribavirin group(P0.05), whereas the converse was true with TLR4(P0.05). Conclusions: We established a FDDHS mouse model showing systemic clinical symptoms. Both HQD and ribavirin can inhibit the expression of CD14 and TLR4 in FDDHS mice, while the effect of ribavirin might be much more violent. The expression changes of CD14 and TLR4 consistently refers to lipopolysaccharide, the commonly and hotly inducing factor in FDDHS.