A novel homozygous mutation in the solute carrier family 12 member 3 gene in a Chinese family with Gitelman syndrome

Loss of function of mutated solute carrier family 12 member 3 (SLC12A3) gene is the most frequent etiology for Gitelman syndrome (GS), which is mainly manifested by hypokalemia, hypomagnesemia and hypocalciuria. We report the genetic characteristics of one suspicious Chinese GS pedigree by gene sequencing. Complete sequencing analysis of the SLC12A3 gene revealed that both the proband and his elder sister had a novel homozygous SLC12A3 mutation: c.2099T>C and p.Leu700Pro. Moreover, the SLC12A3 genes of his mother and daughter encoded the same mutated heterozygote. It was noted that in this pedigree, only the proband complained about recurrent episodes of bilateral lower limb weakness over 8 years, while his elder sister, mother and daughter did not present symptoms. The inconsistent clinical features of this pedigree implied that besides diverse phenotypes possibly originated from the same genotype, gender difference may also dominate the variant GS phenotypes. Further genetic and proteomic research are needed to investigate the precise mechanisms of GS, including the study of specific ethnicities.

Tashinone II A-sulfoacid-natrum elevates the pain threshold through inhibiting nuclear factor kappa B pathway in neuropathic cancer pain.

OBJECTIVE: The purpose of this study was to evaluate the effects of Tashinone II A-sulfoacid-natrum on the pain threshold and potential molecular mechanism for neuropathic cancer pain. METHODS: Forty‑five male Balb/c mice were divided into control group model group and experiment group with each 15. The sciatic nerve muscle plexus of experiment and model group were given injection containing S180 sarcoma cell 2 × 106 mL for each mouse. Mice in the experiment group were given Tashinone II A-sulfoacid-natrum 25 mg/kg once a day intraperitoneal injection. Moreover, mice in the control group were given physiological saline 25 mg/kg, once a day intraperitoneal injection. The mechanical withdraw threshold and thermal withdraw latency were recorded before S180 sarcoma cell injection and in the time point of day 3, 6, 9, 12, and 14. After 14 days treatment, the mice were treated to death and the sciatic nerve CX3CR1 and nuclear factor kappa B (NF‑κB) mRNA was tested by quantitative polymerase chain reaction. RESULTS: Compared with control group, the mechanical and thermal pain threshold of experiment group was significant decreased (P < 0.05). However, compared with the model group, the mechanical, and thermal pain threshold of experiment group was significant elevated in time point of day 3, 6, 9, 12, 14 for mechanical pain threshold and day 9, 12 14 for thermal pain threshold (P < 0.05); the pain threshold for the experiment and model group was decreased in the first 9 days and then elevated gradually. Compared with control group, the CX3CR1 and NF‑κB mRNA relative expression in mice sciatic nerve of experiment group was significant elevated (P < 0.05); but compared with model group, the CX3CR1 and NF‑κB mRNA relative expression of experiment group was significant decreased (P < 0.05). CONCLUSION: Tashinone II A-sulfoacid-natrum can elevates the mechanical and thermal pain threshold through inhibiting the NF‑κB in neuropathic cancer pain rat.

A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model

We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.

Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD.

Current seroprevalence of hepatitis A virus infection among kindergarten children and teachers in Taiwan.

Taiwan was a hyperendemic area for hepatitis A virus (HAV) infection before the late 1980s. The seroprevalence of HAV infection was higher than 90% with most HAV infection occurring during childhood. This study was to estimate the seroprevalence of HAV infection among preschool children in central Taiwan. A community-based survey was carried out in 54 kindergartens in 10 urban areas, 10 rural areas and 2 aboriginal areas randomly selected through stratified sampling. Serum samples of 2,549 healthy preschool children and 104 teachers in study kindergartens were screened for the HAV antibodies (anti-HAV) by means of a commercially available microparticle enzyme immunoassay (AxSYM HAVAB). Among aboriginal kindergarten children, more than 96% of them were anti-HAV seropositive due to a mass HAV vaccination program. In urban and rural areas, kindergarten children had a very low prevalence of anti-HAV (0.4%) in contrast to a high seroprevalence in their teachers (78%). There was no gender difference in seroprevalence of anti-HAV, while the anti-HAV seroprevalence was significantly higher in urban areas than in rural areas. Crowdedness of living in urban areas might facilitate the person-to-person transmission of infectious agents.

Pyomyositis--with special reference to the comparison between extra- and intrapelvic muscle abscess.

Fifteen patients, nine males and six females, diagnosed with pyomyositis from 1988 to 1994, and followed for an average of 69.8 months, were reviewed. Excluding two children, the average age was 56.6 years. Eleven adults (73.3%) had underlying diseases. The lesions were multiple in five patients (33.3%) and a total of twenty-four muscle abscesses, including eleven extrapelvic and thirteen intrapelvic, were identified. When comparing extra- and intrapelvic pyomyositis, intrapelvic pyomyositis presents a diagnostic challenge requiring a high index of suspicion. Distinct clinical features such as local heat and painful swelling were all identified in extrapelvic pyomyositis, but they rarely (in only two of the thirteen lesions) emerged in intrapelvic pyomyositis. The average time from presentation to diagnosis was significantly longer in intrapelvic than in extrapelvic pyomyositis (1.4 vs 9.7 days). Although aspiration showed a high diagnostic rate in extrapelvic muscle abscesses, it was difficult to perform and was occasionally misinterpreted in intrapelvic cases. Routine X-rays were not helpful in making the diagnosis. CT scan was valuable because it provided positive diagnostic findings in all twelve patients who received one. The causative organisms in our patients were Staphylococcus aureus in eight (53.3%), Escherichia coli in three (20%), and Klebsiella in three (20%). Treatments consisted of parenteral antibiotics for all patients, image-guided aspiration in four patients, and surgical drainage in eleven patients. Two intrapelvic pyomyositis patients expired due to sepsis. At the completion of the study, twelve patients were asymptomatic without sequel, and one patient had a recurrence.

Children poisoning in Taiwan.

Poisoning is a well known cause of morbidity and mortality in children. In Taiwan, little information has been published regarding the status of pediatric poisoning exposures. To provide more information on pediatric poisoning exposures for the purpose of poison prevention, a retrospective study was designed and conducted to analyse the data of National Poison Centre (NPC), Taiwan. All telephone inquiries concerning poisoning exposures in those under 19 years of age, received by NPC-Taiwan from July 1985 through December 1993, were included in this study. The age, sex, reason for exposure, route of exposure, substances involved and clinical outcome of those telephone calls were then analyzed. A total of 5,812 inquiries concerning poisoning exposures in children were recorded. Male exposures were more prevalent than females (59%) Vs. 41%) Accidental exposures accounted for 77.7% of the cases and most were exposed by the oral route. Substances most frequently ingested were household products, benzodiazepines and pesticides. The data revealed a mortality rate of 1.4%. Accidental poisoning exposures from household products and drugs remain a significant problem for those younger than 6 years of age. Further education of parents and care takers and the employment of child-resistant containers are needed to prevent cases of pediatric poisoning. Reduction of amphetamine abuse in adolescents is also of major concern and deserves more attention.

Application of deltamethrin-impregnated bednets for mosquito and malaria control in Yunnan, China.

The results of research in China in recent years show that: 1) Different laboratory sensitivity of adult Anopheles minimus, An. sinensis and Culex pipiens quinquefasciatus to deltamethrin exist in Yunnan. Although the range and duration for the use of permethrin and deltamethrin was limited, resistance of An. minimus, An. sinensis and Cx. pipiens quinquefasciatus to different extent in some areas existed. 2) On walls built with cement and covered with a thin layer of lime on which deltamethrin at a dosage of 0.025 g/m2 was sprayed, 100% of the mosquitos were stricken down within 3 days, 80% at the 15th day, 50% at the 20th day. The residual effectiveness on the bamboo and wood walls was good and could last for over 40 days, but on the mud walls a mortality of only 40% on the spraying day was observed, indicating that deltamethrin was not suitable for this purpose. Deltamethrin spraying reduced total caught mosquitos within 30 days, but there was no difference between the effects of deltamethrin (0.025 g/m2) and DDT (2 g/m2) at the 60th day. Deltamethrin effect on reducing densities of endophilic An. vagus, An. culicifacies and exophilic An. philippinensis was better than that of DDT (lasting over 60 days), but its effect on semi-endophilic An. sinensis lasted only 15 days. Against An. mininus, it showed good effects within 20 days but did not last as long as DDT (60 days). Residual deltamethrin and DDT spraying could both control malaria vectors, reduce the infection of infants by malaria, and reduce malaria parasite carrier rates (within 50 days). 3) Laboratory experiments showed that deltamethrin-impregnated bednets at a dosage of 0.015 g/m2 had a positive effect on An. minimus. The residual effect of unwashed deltamethrin-impregnated bednets at a dosage of 0.015 mg/m2 against An. sinensis was apparent and could last for 13 months. When an impregnated bednet was washed for the first time at the 12th month, its mortality effect on An. sinensis was reduced quickly to lower than 50%. The residual effect could last for 2-3 months when washed at the 6th month, but was lost when washed for the second time at the 12th month. 4) The effects of the impregnated-bednets on An. sinensis were different, even opposite, between different investigations. However, the treated bednets caused the density of An. minimus in houses to fall by 67.94%, and the total density in houses and cattle shelters by 67.91%. Moreover, it could shorten the life span of An. minimus. It did not work on the outdoor density of An. minimus. It is necessary to integrate with other measures, for achieving the desired effect.

Ascaris and Trichuris do not contribute to growth retardation in primary school children.

To access the effectiveness of the treatment of soil-transmitted helminthiasis (STH) on the growth of primary school children, 353 children were block stratified to receive either mebendazole plus pyrantel oxantel pamoate every three months or a placebo. The children were followed for two years with 89% completing the trial. Follow-up stools indicated that the treatment was efficacious for ascariasis and trichuriasis. There was virtually no hookworm infection. The children were malnourished as measured by the number below -2 SD of height and weight standards. There was no difference in height or weight between the treatment and control groups by sex initially or at the end of two years of follow-up. The treatment of Ascaris and Trichuris had no effect on growth parameters. The effect of STH on growth may be mediated through hookworm infections.

Detection of blood stage antigens of Plasmodium vivax by sandwich ELISA using pan-species monoclonal antibodies and polyclonal antibodies.

This paper reports an improved PcAb-McAb-ELISA test to detect blood stage Plasmodium vivax antigen in which the plates were coated with rabbit anti-P. cynomolgi polyclonal antibody to capture the antigens in test samples and two monoclonal antibodies, M26-32 and 3F9, were added together to react with the captured antigens. The coincidence rate with this test was 93% with microscopically confirmed P. vivax cases, 97% with normal samples, 95% with microscopically negative fever cases from nonendemic areas and 86% from endemic areas, respectively. The sensitivity was greater than 1 parasite/10(5) RBC.

Microtopography of the surface of adult Schistosoma japonicum-like (Malaysian) as observed by scanning electron microscopy.

The surface of adult Schistosoma japonicum-like (Malaysian) was studied by scanning electron microscopy. The basic pattern of surface microtopography is similar to other strains of S. japonicum as previously reported. However, among male member there are some unique differences in the types, number and distribution of surface papillae and morphology of ridges. Three kinds of papillae were observed: (1) the large fungiform papillae (3.5-4 micron in diameter, most without cilia) are more numerous than in other strains of S. japonicum, they concentrate on the lateral aspect of the anterior and middle parts close to the edge of the gynecophoral canal, and on the dorso-lateral aspect of the posterior part towards the tail tip; (2) the small hemispherical papillae (1.5-2 micron in diameter, all bearing cilia) are especially numerous in the suckers, the gynecophoral canal and parts of the tegument around the suckers and close to the tail tip; on the rest of the surface they are evenly distributed; (3) the cratered papillae (3-4 micron in diameter, about half having cilia) are more numerous than on other strains, they concentrate on the lateral aspect of the middle part and on the edges of the gynecophoral canal. The surface ridges (about 0.2-0.3 micron in width) are tall, highly branching and perforated; they are most developed in the middle part. Spines were observed only in the suckers and the gynecophoral canals. In contrast to the male, the female has numerous spines on all parts of the surface except the most anterior, where a large number of long cilia were observed. All three kinds of papillae were present; fungiform papillae are more numerous than in females of other strains; they concentrate on the latero-dorsal aspect of middle and posterior parts, and around the excretory pore. Ridges are much less developed than in the male and are prominent only in the middle part.

Failure of irradiated Echinostoma audyi and Hypoderaeum dingeri to sensitize Lymnaea rubiginosa snails.

Attempts to induce acquired resistance in Lymnaea rubiginosa snails against the echinostomes Echinostoma audyi and Hypoderaeum dingeri by means of irradiated miracidia were unsuccessful, although Lie and coworkers using similar methods had recently sensitized Biomphalaria glabrata against Echinostoma lindoense (1975a). In contrast to the B. glabrata-E. lindoense system, in Lymnaea rubiginosa the amebocytic response to irradiated parasites was slow: irradiated E. audyi sporocysts were encapsulated 15 to 28 days and H. dingeri sporocysts 20 to 27 days postexposure. No obvious enlargement of the amebocyte-producing organ was seen. No resistance was demonstrable to subsequent homologous challenge. Development of acquired resistance to a trematode infection in snails may be related to the speed with which the snails destroy the irradiated sporocysts.