T-type Ca2+ channels and their relationship with pre-neoplastic and neoplastic lesions in the human breast

The expression of T-type voltage-dependent Ca2+ channels (Cav3) has been previously observed in breast cancer, but their expression and subcellular localization were not evaluated in pre-neoplastic lesions. Therefore, this work aimed to evaluate protein expression and subcellular localization of T-type channel isoforms in human breast tissue samples. Protein expressions of CaV3.1, CaV3.2, and CaV3.3 were evaluated by immunohistochemistry in breast without alteration, in proliferative non-neoplastic lesions, and in neoplastic ductal epithelial lesions of the human breast. CaV3.1, CaV3.2, and CaV3.3 nuclear expressions were decreased in advanced stages of neoplastic transformation, whereas CaV3.1 and CaV3.2 cytoplasmic expression increased. Also, the decrease in nuclear expression was correlated with an increase in cytoplasmic expression for CaV3.1 isoform. The change in CaV3 protein expression and subcellular localization are consistent with the neoplastic transformation stages of mammary epithelial cells, evident in early neoplastic lesions, such as ductal carcinomas in situ. These results suggest a possible involvement of CaV3 in the carcinogenic processes and could be considered as a potential pharmacological target in new therapies for breast cancer treatment.

Mibefradil improves skeletal muscle mass, function and structure in obese mice / 南方医科大学学报

OBJECTIVE@#To observe the effect of mibefradil on skeletal muscle mass, function and structure in obese mice.@*METHODS@#Fifteen 6-week-old C57BL/6 mice were randomized equally into normal diet group (control group), high-fat diet (HFD) group and high-fat diet +mibefradil intervention group (HFD +Mibe group). The grip strength of the mice was measured using an electronic grip strength meter, and the muscle content of the hindlimb was analyzed by X-ray absorptiometry (DXA). Triglyceride (TG) and total cholesterol (TC) levels of the mice were measured with GPO-PAP method. The cross-sectional area of the muscle fibers was observed with HE staining. The changes in the level of autophagy in the muscles were detected by Western blotting and immunofluorescence assay, and the activation of the Akt/mTOR signaling pathway was detected with Western blotting.@*RESULTS@#Compared with those in the control group, the mice in HFD group had a significantly greater body weight, lower relative grip strength, smaller average cross sectional area of the muscle fibers, and a lower hindlimb muscle ratio (P < 0.05). Immunofluorescence assay revealed a homogenous distribution of LC3 emitting light red fluorescence in the cytoplasm in the muscle cells in HFD group and HFD+Mibe group, while bright spots of red fluorescence were detected in HFD group. In HFD group, the muscular tissues of the mice showed an increased expression level of LC3 II protein with lowered expressions of p62 protein and phosphorylated AKT and mTOR (P < 0.05). Mibefradil treatment significantly reduced body weight of the mice, lowered the expression level of p62 protein, and increased forelimb grip strength, hindlimb muscle ratio, cross-sectional area of the muscle fibers, and the expression levels of LC3 II protein and phosphorylated AKT and mTOR (P < 0.05).@*CONCLUSION@#Mibefradil treatment can moderate high-fat diet-induced weight gain and improve muscle mass and function in obese mice possibly by activating AKT/mTOR signal pathway to improve lipid metabolism and inhibit obesityinduced autophagy.

Research progress of T-type calcium channel in cancer / 中国医师杂志

In most non-excited cells, voltage-gated T-type calcium channels present three properties of activation, inactivation and slow inactivation, thus contribute to cellular calcium signaling and membrane potential. By which T-type calcium channels play an important role in many cancer cellular processes such as cell proliferation, differentiation, apoptosis, invasion, and metastasis. Inhibiting T-type calcium channels by drugs or genetic tools can change the related cellular currents and the intracellular Ca 2+ , thereby regulating the biological tumorigenesis. This article reviews the electrophysiological of T-type calcium channels during tumor progression, aims to provide a scientific basis for the study and treatment in cancer.

Sex Differences in Electrophysiological Properties of Mouse Medial Preoptic Area Neurons Revealed by In Vitro Whole-cell Recordings / 神经科学通报·英文版

Despite extensive characterization of sex differences in the medial preoptic area (mPOA) of the hypothalamus, we know surprisingly little about whether or how male and female mPOA neurons differ electrophysiologically, especially in terms of neuronal firing and behavioral pattern generation. In this study, by performing whole-cell patch clamp recordings of the mPOA, we investigated the influences of sex, cell type, and gonadal hormones on the electrophysiological properties of mPOA neurons. Notably, we uncovered significant sex differences in input resistance (male > female) and in the percentage of neurons that displayed post-inhibitory rebound (male > female). Furthermore, we found that the current mediated by the T-type Ca

Effectiveness of volar oblique T-type locking plate and raft screws reduction and fixation in treatment of extreme distal radius fractures / 中国修复重建外科杂志

Objective: To investigate the effectiveness of volar oblique T-type locking plate and raft screws reduction and fixation in the treatment of extreme distal radius fractures. Methods: Between July 2014 and July 2018, 15 patients with extreme distal radius fractures were treated with volar oblique T-type locking plate and raft screws reduction and fixation. There were 6 males and 9 females, aged from 30 to 66 years with an average age of 56.6 years. The cause of injury was falling from height in 2 cases and falling in 13 cases. All of them were fresh closed injuries. The fractures were rated as type 23C1 in 8 cases and as type 23C2 in 7 cases according to AO/Orthopaedic Trauma Association (AO/OTA) classification. There were 7 cases of ulnar styloid process fracture and 2 cases of distal radioulnar joint instability. The time from injury to operation was 6 to 9 days with an average of 7.3 days. The fracture healing and the radial height, palm inclination, and ulnar deviation were observed by X-ray reexamination. Cooney score was used to evaluate the effectiveness. Results: All incisions healed by first intention. All patients were followed up 12-24 months, with an average of 14.6 months. X-ray films showed that all fractures healed, and the healing time ranged from 5 to 10 months, with an average of 8.2 months. No internal fixation failure or secondary fracture displacement occurred. At last follow-up, the radial height, palm inclination, and ulnar deviation recovered well, and the differences between pre- and post-operation were significant ( P<0.05). The pain, function, activity, and grip strength scores and the total score of Cooney score were significantly higher than those before operation ( P<0.05). There were 11 cases of excellent, 3 cases of good, and 1 case of good, with an excellent and good rate of 93%. Conclusion: For extreme distal radius fractures, the volar oblique T-type locking plate and raft screws reduction and fixation can restore the radialheight, palm inclination, and ulnar deviation, fix firmly, and recover the wrist joint function exercise early, and obtain satisfactory effectiveness.

Role of T-type Calcium Channels in Generating Hyperexcitatory Behaviors during Emergence from Sevoflurane Anesthesia in Neonatal Rats / 神经科学通报·英文版

In the current study, we sought to investigate whether T-type Ca channels (TCCs) in the brain are involved in generating post-anesthetic hyperexcitatory behaviors (PAHBs). We found that younger rat pups (postnatal days 9-11) had a higher incidence of PAHBs and higher PAHB scores than older pups (postnatal days 16-18) during emergence from sevoflurane anesthesia. The power spectrum of the theta oscillations (4 Hz-8 Hz) in the prefrontal cortex was significantly enhanced in younger pups when PAHBs occurred, while there were no significant changes in older pups. Both the power of theta oscillations and the level of PAHBs were significantly reduced by the administration of TCC inhibitors. Moreover, the sensitivity of TCCs in the medial dorsal thalamic nucleus to sevoflurane was found to increase with age by investigating the kinetic properties of TCCs in vitro. TCCs were activated by potentiated GABAergic depolarization with a sub-anesthetic dose of sevoflurane (1%). These data suggest that (1) TCCs in the brain contribute to the generation of PAHBs and the concomitant electroencephalographic changes; (2) the stronger inhibitory effect of sevoflurane contributes to the lack of PAHBs in older rats; and (3) the contribution of TCCs to PAHBs is not mediated by a direct effect of sevoflurane on TCCs.

A Computational Modeling Reveals That Strength of Inhibitory Input, E/I Balance, and Distance of Excitatory Input Modulate Thalamocortical Bursting Properties

The thalamus is a brain structure known to modulate sensory information before relaying to the cortex. The unique ability of a thalamocortical (TC) neuron to switch between the high frequency burst firing and single spike tonic firing has been implicated to have a key role in sensory modulation including pain. Of the two firing modes, burst firing, especially maintaining certain burst firing properties, was suggested to be critical in controlling nociceptive behaviors. Therefore, understanding the factors that influence burst firing properties would offer important insight into understanding sensory modulation. Using computational modeling, we investigated how the balance of excitatory and inhibitory inputs into a TC neuron influence TC bursting properties. We found that intensity of inhibitory inputs and the timing of excitatory input delivery control the dynamics of bursting properties. Then, to reflect a more realistic model, excitatory inputs delivered at different dendritic locations—proximal, intermediate, or distal—of a TC neuron were also investigated. Interestingly, excitatory input delivered into a distal dendrite, despite the furthest distance, had the strongest influence in shaping burst firing properties, suggesting that not all inputs equally contribute to modulating TC bursting properties. Overall, the results provide computational insights in understanding the detailed mechanism of the factors influencing temporal pattern of thalamic bursts.

T-Type Calcium Channels Are Required to Maintain Viability of Neural Progenitor Cells

T-type calcium channels are low voltage-activated calcium channels that evoke small and transient calcium currents. Recently, T-type calcium channels have been implicated in neurodevelopmental disorders such as autism spectrum disorder and neural tube defects. However, their function during embryonic development is largely unknown. Here, we investigated the function and expression of T-type calcium channels in embryonic neural progenitor cells (NPCs). First, we compared the expression of T-type calcium channel subtypes (CaV3.1, 3.2, and 3.3) in NPCs and differentiated neural cells (neurons and astrocytes). We detected all subtypes in neurons but not in astrocytes. In NPCs, CaV3.1 was the dominant subtype, whereas CaV3.2 was weakly expressed, and CaV3.3 was not detected. Next, we determined CaV3.1 expression levels in the cortex during early brain development. Expression levels of CaV3.1 in the embryonic period were transiently decreased during the perinatal period and increased at postnatal day 11. We then pharmacologically blocked T-type calcium channels to determine the effects in neuronal cells. The blockade of T-type calcium channels reduced cell viability, and induced apoptotic cell death in NPCs but not in differentiated astrocytes. Furthermore, blocking T-type calcium channels rapidly reduced AKT-phosphorylation (Ser473) and GSK3β-phosphorylation (Ser9). Our results suggest that T-type calcium channels play essential roles in maintaining NPC viability, and T-type calcium channel blockers are toxic to embryonic neural cells, and may potentially be responsible for neurodevelopmental disorders.

Effects of thyroid hormone on myocardial T-type calcium channels at mRNA and protein levels in rats / 中国病理生理杂志

AIM:To observe the effect of thyroxine on the expression of T-type calcium channels Cav3. 1, Cav3. 2 and Cav3. 3 in rat myocardium, and to explore the possible biological mechanism between the changes of the ex-pression of T-type calcium channels and the arrhythmia in hyperthyroid heart disease. METHODS:Healthy SD rats (n=20) were randomly divided into normal control group (n=10) and hyperthyroid heart disease group (n=10). The animal model was established by intraperitoneal injection of levothyroxine for 35 d. The contents of T3 and T4 in serum, the heart-to-body weight ratio, the diameter of cardiac myocytes and electrocardiograph were measured to evaluate hyperthyroid heart disease. Moreover, the mRNA and protein expression levels of T-type calcium channels in the myocardium were measured by RT-PCR, immunohistochemistry and Western blot. RESULTS:After intraperitoneal injection of levothyroxine for 35 d, compared with the normal control group, the serum contents of T3 and T4, the heart-to-body weight ratio and the diameter of cardiac myocytes were significantly increased in hyperthyroid heart disease group (P<0.05), and arrhythmia occurred in hyperthyroid heart disease group. By immunohistochemistry and Western blot, the protein expression of Cav3. 1 in-creased significantly (P<0.05), while the protein expression of Cav3.2 decreased significantly (P<0.01). However, no change of the Cav3. 3 protein was observed. The results of RT-PCR were the same as immunohistochemistry and Western blot. CONCLUSION:Thyroxine promotes the expression of Cav3. 1 in the myocardium but inhibits the expression of Cav3. 2 at mRNA and protein levels, which might be involved in arrhythmia in hyperthyroid heart disease.

Role of T-type calcium channels in up-regulation of spinal CaMKⅡ expression in rats with neuro-pathic pain / 中华麻醉学杂志

Objective To evaluate the role of T?type calcium channels in up?regulation of spinal Ca2+∕calmodulin?dependent protein kinase Ⅱ ( CaMKⅡ) expression in rats with neuropathic pain. Meth?ods Forty?eight male Sprague?Dawley rats, weighing 230-270 g, in which intrathecal catheters were suc?cessfully implanted, were divided into 4 groups ( n=12 each) using a random number table: sham opera?tion group (group S), neuropathic pain group (group NP), normal saline group (group NS), and T?type calcium channel blocker mibefradil group ( group M ) . The model of neuropathic pain was established by chronic compression of the dorsal root ganglion ( DRG) . Normal saline 20μl and mibefradil 200μg ( dilu?ted to 20μl in normal saline) were injected intrathecally at 5 days after compression of the DRG in NS and M groups, respectively. Before intrathecal catheter implantation ( T1 ) , before compression of the DRG ( T2 ) , at 5 days after compression of the DRG and before intrathecal administration ( T3 ) , and at 30, 60, 120 and 240 min after intrathecal administration ( T4?7 ) , the mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal latency ( TWL) were measured. The rats were sacrificed after the last measure?ment of the pain threshold at T7 , and the lumbar enlargement segments of the spinal cord were harvested for determination of CaMKⅡ expression by Western blot. Results Compared with group S, the MWT was significantly decreased, and TWL was significantly shortened at T3?7 , and the expression of spinal CaMKⅡ was significantly up?regulated in NP and M groups (P0.05). Conclusion T?type calcium channels are opened, the intra?cellular free calcium ion concentrations are increased, and activated spinal CaMKⅡ is involved in the de?velopment of neuropathic pain in rats.

Enhancement of T-type Ca2+ channel currents in dorsal root ganglia neurons by nesfatin-1 and possible mechanisms / 中华老年医学杂志

Objective To investigate the effect of nesfatin-1 (NSF-1) on T-type Ca2+ channel currents in adult mouse dorsal root ganglion (DRG) neurons and possible signal transduction mechanisms involved.Methods We measured the expression of melanocortin 4 receptors(MC4-R)in mouse DRG by using western blotting analysis.The whole-cell patch clamp technique was used to record the effects of NSF 1 on T-type Ca2+ channel currents in small DRG neurons and several ligands were experimented to further clarify relevant signaling pathways.Results MC4-Rs were abundantly expressed in DRG neurons.NSF-1 enhanced T-type calcium channel currents in a dose-dependent manner in small DRG neurons in mice.NSF-1 mediated increment of T-type calcium channel currents was blocked by the MC4-R antagonist HS024,phosphokinase C antagonists GF109203X,and chelerythrine chloride,while the blockade of phospohokinase A PKI 6-22 elicited no such effects.Conclusions NSF-1 can enhance T type calcium channel currents in small DRG neurons through an MC4-R-dependent PKC signaling pathway.

T type calciumchannel activated by brain injury induces neural stem cell proliferation / 西安交通大学学报(医学版)

ABSTRACT:Objective To investigate the mechanism and induction of T type calcium channel on neural stem cells after brain injury .Methods Adult mice brain injury model was established and divided into control ,sham operation ,surgery ,and surgery+mebefradil groups .Neural stem cells were separated from the subventricular zone (SVZ) and identified .Moreover ,we analyzed the results using MTT and neural stem cell sphere counting after adding different doses of mibefradil in culture medium ,respectively .Then we calculated the half maximal inhibitory concentration (IC50) of mibefradil on neural stem cells .Finally ,we analyzed the expression of Cav3 .2 in SVZ and the protein expressions of Cav3 .2 ,Cyclin A and caspase‐3 in neural stem cells by Western blot .Results In vivo , neural stem cell proliferation was increased in surgery group compared with that in control and sham‐operation groups .The proliferation of neural stem cells in surgery + mibefradil groups was significantly decreased compared with that in surgery group after mibefradil‐induced inhibition of T type calcium channel protein . In vitro , the formation of neural stem cell sphere was significantly inhibited after adding mibefradil .The cell growth ratio was significantly decreased when the concentration of mibefradil was above 5μmol/L .A values in 5 μmol/L ,10 μmol/L and 20μmol/L groups were significantly lower than those in control group (P<0 .05) .IC50 was 8 .93μmol/L .The protein expressions of Cyclin A and Cav3 .2 were inhibited while that of caspase‐3 was increased after mibefradil treatment .Conclusion Neural stem cell proliferation was enhanced by activating T type calcium channel after brain injury .

Mibefradil reduces blood glucose concentration in db/db mice

OBJECTIVE: Numerous recent studies suggest that abnormal intracellular calcium concentration ([Ca2+]i) is a common defect in diabetic animal models and patients. Abnormal calcium handling is an important mechanism in the defective pancreatic β-cell function in type 2 diabetes. T-type Ca2+ channel antagonists lower blood glucose in type 2 diabetes, but the mechanism remains unknown. METHODS: We examined the effect of the Ca2+ channel antagonist mibefradil on blood glucose in male db/db mice and phenotypically normal heterozygous mice by intraperitoneal injection. RESULTS: Mibefradil (15 mg/kg, i.p., b.i.d.) caused a profound reduction of fasting blood glucose from 430.92±20.46 mg/dl to 285.20±5.74 mg/dl in three days. The hypoglycemic effect of mibefradil was reproduced by NNC 55-0396, a compound structurally similar to mibefradil but more selective for T-type Ca2+ channels, but not by the specific L-type Ca2+ channel blocker nicardipine. Mibefradil did not show such hypoglycemic effects in heterozygous animals. In addition, triglycerides, basal insulin and food intake were significantly decreased by mibefradil treatment in the db/db mice but not in the controls. Western blot analysis, immunohistochemistry and immunofluorescence staining showed a significantly increased expression of T-type Ca2+ channel α-subunits Cav3.1 and Cav3.2 in liver and brain tissues from db/db mice compared to those from heterozygous animals. CONCLUSIONS: Collectively, these results suggest that T-type Ca2+ channels are potential therapeutic targets for antidiabetic drugs. .

A system review: the effects of T-type CCB or ACEI /ARB for hypertensive patients with chronic kidney disease / 中国药学杂志

OBJECTIVE: To evaluate whether T-type CCBs are equivalent with or superior to ACEIs/ARBs on renal outcomes in hupertensive patients with chronic kidney disease. METHODS: Cochrane Library, Pubmed, EMbase and CNKI were searched for relevant randomized controlled trials (RCTs) from inception to May 2012. The meta-analysis was performed by Revman 5.1 software. RESULTS: Five RCTs (563 subjects) were included in the present study. T-type CCBs performed a pooled improvement in creatinine clearance and glomerular filtration rate similar to ACEIs/ARBs but were inferior to ACEIs/ARBs on reducing proteinuria excretion (three RCTs, 389 subjects, WMD 0.26 g·d-1, 95% CI 0.10 to 0.43), although T-type CCBs and ACEIs/ARBs showed stable anti-hypertensive effect. CONCLUSION: Our findings suggest that despite T-type CCBs do offer salutary effects on kidney outcomes and hypertension can be applied to treat hypertensive patients with chronic kidney disease, ACEIs /ARBs might be better choice for pressure control in this target population especially when proteinuria is the main issue of renal dysfunction.

Progress in modulation of T-type calcium channels by ;G protein-coupled receptors / 中国药理学通报

T-type calcium channels are expressed in various tis-sues and play key roles in physiology and pathophysiology,inclu-ding neuronal firing,hormone secretion,pain,and cancer,etc. Hence,it is critical to understand the molecular mechanisms un-derlying the regulation of T-type channels.Substantial literature suggests many G protein-coupled receptors (GPCRs)and related second messengers can modulate T-type channel in some extent. Here,this review focuses on the modulation of T-type calcium channels by GPCRs and related second messengers.

Long-Term Potentiation of Excitatory Synaptic Strength in Spinothalamic Tract Neurons of the Rat Spinal Cord

Spinal dorsal horn nociceptive neurons have been shown to undergo long-term synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD). Here, we focused on the spinothalamic tract (STT) neurons that are the main nociceptive neurons projecting from the spinal cord to the thalamus. Optical technique using fluorescent dye has made it possible to identify the STT neurons in the spinal cord. Evoked fast mono-synaptic, excitatory postsynaptic currents (eEPSCs) were measured in the STT neurons. Time-based tetanic stimulation (TBS) was employed to induce long-term potentiation (LTP) in the STT neurons. Coincident stimulation of both pre- and postsynaptic neurons using TBS showed immediate and persistent increase in AMPA receptor-mediated EPSCs. LTP can also be induced by postsynaptic spiking together with pharmacological stimulation using chemical NMDA. TBS-induced LTP observed in STT neurons was blocked by internal BAPTA, or Ni2+, a T-type VOCC blocker. However, LTP was intact in the presence of L-type VOCC blocker. These results suggest that long-term plastic change of STT neurons requires NMDA receptor activation and postsynaptic calcium but is differentially sensitive to T-type VOCCs.

Role of T-type calcium channel in spinal neurotoxicity of intrathecal lidocaine in rats / 中华麻醉学杂志

ObjectiveTo investigate the role of T-type calcium channel in the spinal neurotoxicity of intrathecal (IT) lidocaine in rats.MethodsForty-eight adult male SD rats in which IT catheter was successfully implanted,weighing 230-270 g,were randomly divided into 4 groups ( n =12 each):dimethyl sulfoxide (DMSO)group (group D),lidocaine group (group L),mibefradil + lidocaine group (group M),normal saline + lidocaine group (group N).Another 12 rats served as control group (group C).DMSO and 10％ lidocaine 20μl were injected intrathecally in groups D and L respectively.After mibefradil 200 μg/10μl and normal saline 10 μl were injected intrathecally in groups M and N respectively,10％ lidocaine 20 μl was injected intrathecally in the two groups.The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured before IT injection and at 2,4,8 and 12 h and 1,2,3,4 and 5 d after IT injection (T0-9).Four rats were sacrificed at T6 in each group and their lumbar enlargements were removed for microscopic examination.ResultsCompared with group C,no significant change in MWT and TWL was found at each time point in group D,MWT was significantly increased at T1-8 and TWL was significantly prolonged at T1-7 in groups L and N,and MWT was significantly increased at T1-6 and TWL was significantly prolonged at T1-6 in group M ( P ＜ 0.05 ).Compared with groups L and N,MWT was significantly decreased at T1-4 and TWL was significantly shortened at T1-4 in group M ( P ＜ 0.05).Pathological injury was significantly reduced in group M as compared with groups L and N.ConclusionT-type calcium channel is involved in the spinal neurotoxicity of IT lidocaine in rats.

T-type calcium channels and tumor proliferation / 国际肿瘤学杂志

Expression of the T-type Ca2 + channels has been reported in numerous types of tumors due to their unique activation/inactivation properties. In some cancer cells, the expression of T-type Ca2+ channels is proliferation state dependent. T-type channel blockers or interfering the α1 subunit of this channel via siRNA decrease proliferation of these cells. Since T-type Ca2+ channels are not expressed in epithelial cells, selective T-type Ca2 + channel blockers maybe serve as a potential therapeutic approach in the treatment of certain types of cancers.

Vasorelaxant effects of calcium channel blockers on isolated thoracic aortic rings from thyroxine-induced hypertensive rats / 中国药理学通报

Aim To investigate the effects of T-and L-type calcium channel blockers on isolated thoracic aorta from thyroxine-induced hypertensive rats.Methods Hyperthyroidism was induced by administering L-thyroxine (T4,0.5 mg·kg~(-1),sc) daily for 16 days.Sham-treated euthyroid control rats were only received vehicle saline for 16 days. Experiments were performed in isolated thoracic aorta rings from euthyroid and hyperthyroid rats. Mibefradil and diltiazem were used to inhibit T-and L-type calcium channels,respectively.Results Thyroid hormone excess for 16 days induced characteristic changes in body weight,heart rate and systolic blood pressure in rats. The body weight was significantly decreased,heart rate and systolic blood pressure were increased in T4-treated rats. Thoracic aorta morphology was altered in T4-treated rats. The thickness of adventitia was increased with hypertrophy and hyperplasia of the smooth musle cells in T4-treated rats. Vasorelaxant effect of T-and L-type calcium channel blockers were accentuated in aortic rings from T4-treated rats.Conclusion These data suggest that T-and L-type calcium channels are functionally upregulated in isolated thoracic aorta from hyperthyroid rats and they,may be a therapeutic target in thyroxine-induced hypertension.

T Types, emm Genotypes and Antibiotic Resistance of Streptococcus pyogenes Isolated fromSchool Children in Jinju, 2006 / 대한임상미생물학회지

BACKGROUND: Streptococcus pyogenes is the most common cause of bacterial pharyngitis. T antigens and emm genotypes are essential markers for an epidemiological study of S. pyogenes. Macrolide resistance of S. pyogenes is a serious obstracle to successfully treating a sore throat. METHODS: One-hundred forty-seven strains of S. pyogenes isolated from healthy school children in 2006 were subjected to T typing and emm genotyping. A disk diffusion method was applied for several antibiotics. A double disk diffusion test was performed to evaluate the phenotype distribution of macrolide resistance. RESULTS: Among T antigens and emm genotypes, T11 (19.7%) and emm78 (16.7%), respectively, were the most common in 2006. Both T5/27/44 (2.3%) and emm44/61 (9.1%) declined to a great extent from about 29% in 2004. The rate of resistance to antibiotics were 11.6% to erythromycin, 4.8% to clindamycin, 21.8% to tetracycline, and 7.5% to ofloxacin. M and cMLSB phenotypes were 52.9% and 41.2% respectively. CONCLUSION: T typing and emm genotyping proved a dynamic change in their distribution in 2006 compared to the results of 2004. Erythromycin and clindamycin resistance remained low as in 2004, whereas ofloxacin resistance increased slightly. M and cMLSB phenotypes were equivalent in 2006, whereas cMLSB was predominant in 2004.