[Classification, diagnosis and treatment status of pulmonary hypertension from 2012 to 2019: a single center study in Yunnan province].

Objective: To analyze the classification, diagnosis and treatment status of patients with pulmonary hypertension (PH) in Yunnan province. Methods: This was a retrospective study. Hospitalized patients with PH at Yan'an Affiliated Hospital of Kunming Medical University from January 2012 to December 2019 were enrolled. The clinical data of enrolled patients, including demographic data, comorbidities, targeted drug therapy, echocardiography and right heart catheterization results, were obtained through the electronic medical record system. The composition ratio of PH, diagnosis and treatment were analyzed. Results: A total of 13 590 patients with PH were enrolled, accounting for 3.09% (13 590/440 056) of the total number of hospitalizations during the same period. The composition of PH was predominantly pulmonary arterial hypertension (PAH) (55.50% (7 542/13 590)), followed by pulmonary hypertension (PH) caused by left heart disease (24.16% (3 284/13 590)). Among them, PAH could be subdivided into four types: idiopathic pulmonary arterial hypertension (IPAH), PAH associated with connective tissue disease, PAH associated with portal hypertension, and PAH associated with congenital heart disease (CHD-PAH), with CHD-PAH as the predominating type (98.09% (7 398/7 542). Patients with PAH were predominantly adolescents. In hospitalized patients with PH, from 2012 to 2019, the proportion of children and adolescents showed a decreasing trend from year to year, and the proportion of middle-aged and older adults showed a significant increasing trend, and the proportion of female patients showed a gradual decreasing trend, and the proportion of patients with comorbid hypertension, diabetes mellitus, coronary artery disease, arrhythmia, and pneumonia showed an increasing trend. A total of 1 034 patients (7.61% (1 034/13 590)) underwent right heart catheterization. The concordance rate between echocardiographic and right heart catheterization findings was (86.98% (875/1 006)). A total of 2 574 (18.94%) of PH patients were treated with PAH targeted drugs, of which 58.16% (1 497/2 574) were treated with monotherapy. Among the PH patients treated with PAH targeted drugs, the majority of patients were PAH patients (86.44% (2 225/2 574)), and 83.53% (2 150/2 574) patients treated with PAH targeted drugs were CHD-PAH. Conclusions: Hospitalized PH patients in our center between 2012 and 2019 are predominantly CHD-PAH, and the proportion of patients receiving right heart catheterization and targeted drug therapy is relatively low. The percentage of middle-aged and elderly PH patients shows an increasing trend from year to year, as well as the percentage of those with concomitant comorbidities.

Characterization of the iron oxide phases formed during the synthesis of core-shell FexOy@C nanoparticles modified with Ag.

Core-shell FexOy@C nanoparticles (NPs) modified with Ag were studied with x-ray diffraction, transmission electron microscopy, energy dispersive elemental mapping, Mössbauer spectroscopy, static magnetic measurements, and optical magnetic circular dichroism (MCD). FexOy@C NPs synthesized by the pyrolysis process of the mixture of Fe(NO3)3 · 9H2O with oleylamine and oleic acid were added to a heated mixture of oleylamine and AgNO3 in different concentrations. The final product was a mixture of iron oxide crystalline NPs in an amorphous carbon shell and Ag crystalline NPs. The iron oxide NPs were presented by two magnetic phases with extremely close crystal structures: Fe3O4 and γ-Fe2O3. Ag is shown to form crystalline NPs located very close to the iron oxide NPs. An assumption is made about the formation of hybrid FexOy@C-Ag NPs. Correlations were obtained between the Ag concentration in the fabricated samples, their magnetic properties and the MCD spectrum shape. Introducing Ag led to a approximately linear decrease of the NPs saturation magnetization depending upon the Ag concentration, it also resulted into the MCD spectrum shift to the lower light wave energies. MCD was also studied for the Fe3O4@C NPs synthesized earlier with the same one-step process using different heat treatment temperatures, and MCD spectra were compared for two series of NPs. A possible contribution of the surface plasmon excitation in Ag NPs to the MCD spectrum of the FexOy@C-Ag NPs is discussed.

Predictive value of nodal maximum standardized uptake value of pretreatment [18F]fluorodeoxyglucose positron emission tomography imaging in patients with esophageal cancer.

We retrospectively reviewed 102 patients with esophageal cancer (97.1% squamous cell carcinoma, 96.1% stage III) received FDG-PET staging and were treated by chemoradiotherapy with or without resection to assess whether the pretreatment [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) maximum standardized uptake value (SUVmax) of the primary tumor and metastatic lymph nodes can predict the prognosis of patients with esophageal cancer. Receiver operating characteristic analysis was performed to find the cutoff values for primary tumor SUVmax and nodal SUVmax. The influence of clinical factors including primary tumor SUVmax and nodal SUVmax on local progression-free survival, nodal progression-free survival (NPFS), distant metastases-free survival (DMFS), and overall survival (OS) were evaluated using univariate and multivariate analyses. A total of 40 patients received esophagectomy after neoadjuvant chemoradiotherapy (trimodality), while 62 patients received definitive chemoradiotherapy (dCRT). The median follow-up was 26.4 months. The SUVmax of primary tumor had no significant predictive value on all outcomes, while the SUVmax of metastatic lymph nodes had predictive value on several outcomes. High nodal SUVmax (≥7) predicted for worse outcomes than low nodal SUVmax (<7) in the patients who received dCRT (two-year DMFS, 17% vs. 92%, P < 0.001; NPFS, 14% vs. 81%, P = 0.001; OS, 21% vs. 50%, P = 0.003), but not in those received trimodality. On multivariate analysis of patients receiving dCRT, nodal SUVmax was the strongest independent predictor on DMFS (hazard ratio [HR] 13.93, P < 0.001), NPFS (HR 3.99, P = 0.026), PFS (HR 2.90, P = 0.003), and OS (HR 3.80, P = 0.001). High pretreatment nodal SUVmax predicts worse treatment outcomes for the patients treated with dCRT.

Deletion of crhr2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2.

Corticotropin-releasing hormone (Crh), a 41-residue polypeptide, activates two G-protein-coupled receptors, Crhr1 and Crhr2, causing (among other transductional events) phosphorylation of the transcription factor Creb. The physiologic role of these receptors is only partially understood. Here we report that male, but not female, Crhr2-deficient mice exhibit enhanced anxious behaviour in several tests of anxiety in contrast to mice lacking Crhr1. The enhanced anxiety of Crhr2-deficient mice is not due to changes in hypothalamic-pituitary-adrenal (HPA) axis activity, but rather reflects impaired responses in specific brain regions involved in emotional and autonomic function, as monitored by a reduction of Creb phosphorylation in male, but not female, Crhr2-/- mice. We propose that Crhr2 predominantly mediates a central anxiolytic response, opposing the general anxiogenic effect of Crh mediated by Crhr1. Neither male nor female Crhr2-deficient mice show alterations of baseline feeding behaviour. Both respond with increased edema formation in response to thermal exposure, however, indicating that in contrast to its central role in anxiety, the peripheral role of Crhr2 in vascular permeability is independent of gender.

Toxic effects of two brominated flame retardants BDE-47 and BDE-183 on the survival and protein expression of the tubificid Monopylephorus limosus.

The toxic effects of two brominated diphenyl ethers (BDE), BDE-47, and BDE-183, on a benthic oligochaete tubificid, Monopylephorus limosus were studied under laboratory conditions. Investigated responses included survival, growth, and protein expression profiles, at BDE concentrations of 1, 10, 100, and 700 ng/g on a dry soil weight basis, with isooctane as the carrier solvent. Body weight losses among treatments were insignificant after 8 weeks of exposure. The 8-wk LC(50) of BDE-47 and -183 were 2311 and 169 ng/g, respectively. By applying multivariate analysis techniques, protein expression patterns were compared and correlated with stressful sources of long-term culture, carrier solvent, BDE-47 and -183. The treatment of 8-wk 100 ng/g BDE-47 was most closely clustered to the 10 ng/g BDE-183 treatment, based on the 40 examined protein spots. This indicated that BDE-183 was more potent to M. limosus, than was BDE-47. The 2-wk and 8-wk controls clustered into different groups indicating the occurrence of physiological changes due to long-term laboratory culture. Additionally, solvent effect was shown by grouping the isooctane carrier to different clusters. With further characterization by principle component analysis, it was found that the separation was mainly contributed by the 2nd principal-component. And, the primarily inhibitory variation was at spots 2 (UMP-CMP kinase) and 40 (plasma retinol-binding protein precursor) in the 8-wk groups. On the contrary, protein spots 16 (cell division control protein 2 homolog) and 24 (mitochondrial DNA mismatch repair protein) showed stimulatory variation. In all, the observed proteomic responses suggest that BDEs disrupted metabolic function in M. limosus and multivariate analysis tool offers significant potential for the assessment of various stress sources at biochemical level.

Photoconduction mechanism of oxygen sensitization in InN nanowires.

The photoconduction (PC) mechanism in indium nitride (InN) nanowires (NWs) has been investigated via environment-, temperature-, and power-dependent measurements. The adsorbed oxygen-induced modulation of the surface state is proposed to be the leading factor in the long lifetime or high gain transport and in sensitizing photocurrent generation in the InN NWs. The electron trapping effect by adsorbed oxygen can be verified by the increased activation energy from 33 ± 4 (in vacuum) to 58 ± 2 meV (in oxygen). The observed supralinear power dependence of photocurrent also suggests the presence of acceptor states that influence the carrier recombination behavior and compensate the thermal carriers in the InN NWs. The potential influence of native oxide on the molecule-sensitive PC in this nitride nanomaterial is also inferred.

Antinociceptive potentiation and attenuation of tolerance by intrathecal ß-arrestin 2 small interfering RNA in rats.

BACKGROUND: Tolerance to the analgesic effect of opioids complicates the management of persistent pain states. We tested whether the intrathecal infusion of small interfering RNA (siRNA) against ß-arrestin 2 would reduce tolerance to chronic morphine use and the severity of precipitated morphine withdrawal. METHODS: Intrathecal ß-arrestin 2 (2 µg siRNA per 10 µl per rat) was injected once daily for 3 days. Rats then received a continuous intrathecal infusion of morphine (2 nmol h⁻¹) or saline for 7 days. Daily tail-flick (TF) and intrathecal morphine challenge tests were performed to assess the effect of intrathecal ß-arrestin 2 siRNA on antinociception and tolerance to morphine. Naloxone withdrawal (2 mg kg⁻¹) was performed to assess morphine dependence. RESULTS: In the daily TF test, the antinociception of intrathecal morphine was increased and maintained in rats receiving ß-arrestin 2 siRNA compared with the control group (morphine alone). In the probe response test, rats receiving morphine infusion with ß-arrestin 2 siRNA treatment showed a significant left shift in their dose-response curve, as measured by per cent maximal possible effect (MPE), such that the AD50 was significantly decreased by a factor of 5.6 when compared with that of morphine-infused rats. In the naloxone-induced withdrawal tests, rats receiving ß-arrestin 2 siRNA injection with morphine infusion showed a significant reduction in four of the six signs of withdrawal. CONCLUSIONS: We show here that intrathecal ß-arrestin 2 siRNA in rats enhances analgesia and attenuates naloxone-induced withdrawal symptoms. This may warrant further investigation in the context of long-term use of intrathecal opioids for controlling chronic pain.

Expression cloning of human EGF receptor complementary DNA: gene amplification and three related messenger RNA products in A431 cells.

In order to further define the mechanisms by which polypeptide growth factors regulate gene transcription and cellular growth, expression cloning techniques were used to select human epidermal growth factor (EGF) receptor complementary DNA clones. The EGF 3' coding domain shows striking homology to the transforming gene product of avian erythroblastosis virus (v-erbB). Over-expression of EGF receptors in A431 cell lines correlates with increased EGF receptor mRNA levels and amplification (up to 110 times) of the apparently singular EGF receptor gene. There appear to be three cytoplasmic polyadenylated RNA products of EGF receptor gene expression in A431 cells, one of which contains only 5' (EGF binding domain) sequences and is postulated to encode the secreted EGF receptor-related protein.

Epigenetic suppression of potassium-chloride co-transporter 2 expression in inflammatory pain induced by complete Freund's adjuvant (CFA).

BACKGROUND: Multiple mechanisms contribute to the stimulus-evoked pain hypersensitivity that may be experienced after peripheral inflammation. Persistent pathological stimuli in many pain conditions affect the expression of certain genes through epigenetic alternations. The main purpose of our study was to investigate the role of epigenetic modification on potassium-chloride co-transporter 2 (KCC2) gene expression in the persistence of inflammatory pain. METHODS: Persistent inflammatory pain was induced through the injection of complete Freund's adjuvant (CFA) in the left hind paw of rats. Acetyl-histone H3 and H4 level was determined by chromatin immunoprecipitation in the spinal dorsal horn. Pain behaviour and inhibitory synaptic function of spinal cord were determined before and after CFA injection. KCC2 expression was determined by real time RT-PCR and Western blot. Intrathecal KCC2 siRNA (2 µg per 10 µL per rat) or HDAC inhibitor (10 µg per 10 µL per rat) was injected once daily for 3 days before CFA injection. RESULTS: Persistent inflammatory pain epigenetically suppressed KCC2 expression through histone deacetylase (HDAC)-mediated histone hypoacetylation, resulting in decreased inhibitory signalling efficacy. KCC2 knock-down caused by intrathecal administration of KCC2 siRNA in naïve rats reduced KCC2 expression in the spinal cord, leading to sensitized pain behaviours and impaired inhibitory synaptic transmission in their spinal cords. Moreover, intrathecal HDAC inhibitor injection in CFA rats increased KCC2 expression, partially restoring the spinal inhibitory synaptic transmission and relieving the sensitized pain behaviour. CONCLUSION: These findings suggest that the transcription of spinal KCC2 is regulated by histone acetylation epigenetically following CFA. SIGNIFICANCE: Persistent pain suppresses KCC2 expression through HDAC-mediated histone hypoacetylation and consequently impairs the inhibitory function of inhibitory interneurons. Drugs such as HDAC inhibitors that suppress the influences of persistent pain on the expression of KCC2 may serve as a novel analgesic.

Induction of connexin 37 expression in a rat model of neuropathic pain.

Activation of cutaneous C-fibers by capsaicin or sciatic nerve transection increases the number of astrocytic gap junctions as well as the levels of connexin 43 in the dorsal horn on the stimulated side. Changes in connexin 37 mRNA expression following nerve injury have not been previously documented. We examined the role of gap junction protein connexin 37 in neuropathic hypersensitivity following peripheral nerve injury. Study results showed ipsilaterally increased connexin 37 mRNA levels proximally and distally in rat sciatic nerves after injury and behavioral thermal hyperalgesia at 7 and 14 days. Proximal and distal connexin 37 mRNA levels returned to baseline by 21 days. Sciatic nerve connexin 37 mRNA increases were proportional to the extent of thermal hyperalgesia, but skin, muscle, and lumbar spinal cord connexin 37 mRNA showed no significant changes. Neuropathic pain relief correlated with downregulation of connexin 37 mRNA. Results indicate that upregulation of connexin 37 mRNA following sciatic nerve injury correlates with subsequent thermal hyperalgesia, which suggests that gap junctions (connexin 37) are responsible for the hyperexcitability following peripheral nerve injury.

Intrathecal magnesium sulfate attenuates algogenic behavior and spinal amino acids release after kainic acid receptor activation in rats.

Activation of N-methyl-D-asparate (NMDA) receptor and non-NMDA classes of glutamate receptors play a key role in spinal nociceptive processing. Using with a lumbar intrathecal (IT) catheter and a loop dialysis catheter in lightly anesthetized (1% isoflurane) rats, the effect of IT pre-treatment with magnesium sulfate (100, 300 or 500 microg) on IT kainic acid (KA: 1 microg; non-NMDA receptor agonist) evoked amino acids (AAs) release and corresponding behavior was examined. IT KA produced significant increases (mean+/-SD of % baseline concentration) in dialysate concentrations of aspartate (424+/-88%), glutamate (241+/-35%) and taurine (398+/-58%). IT pre-treatment with MgSO(4) resulted in a dose-dependent suppression of the evoked algogenic behavior and aspartate release. These data suggest that activation of spinal KA receptors provides a powerful stimulus for secondary spinal excitatory AAs release and corresponding appearance of pain behavior. The regulation of this release by magnesium suggests the possible role of this divalent cation in regulating this excitatory effect of non-NMDA receptor activation.

Changes in the levels of nitric oxide synthase and protein kinase C gamma following kainic acid receptor activation in the rat spinal cord.

In this study, we evaluated the levels of nitric oxide synthase, both neuronal and induced (nNOS and iNOS, respectively), cyclooxygenase-1 and 2 (COX-1 and COX-2) and protein kinase C gamma (PKCgamma) and correlated these with algogenic behavior following spinal kainic acid (KA) receptor activation in rats. Thirty adult male Sprague-Dawley rats were randomly assigned into six groups (n=5). Groups A, B, and C received 0.5 g kainic acid intrathecally and were analyzed at 3, 6, 24 h after injection, respectively. Groups D, E, and F received saline and were analyzed at 3, 6, 24 h after injection, respectively. We observed for behavioral changes in the rats following intrathecal KA injection and analyzed the protein levels of NOS, COX and PKCgamma by Western blotting techniques. Importantly, we clarified the potential roles of PKCgamma in the regulation of nNOS and COX-2 following intrathecal injection with KA in the rat spinal cord. COX-2 protein was detected but not significantly changed in the lumbosacral spinal cord at 3, 6, and 24 h following intrathecal KA injection (P>0.05). In contrast, nNOS protein was detected at higher levels in comparison with normal spinal cord at 6 and 24 h after intrathecal administration of KA (P<0.05). PKCgamma also increased significantly at 3, 6, and 24 h after intrathecal KA injection when compared with the baseline level (P<0.05). On the other hand, COX-1 and iNOS were not detected in either normal or KA treated spinal cords. These results provide strong in vivo evidence to support the idea that nNOS but not COX-2, plays an important role in spinal KA receptor activation. Furthermore, up-regulation of PKCgamma is involved in KA induced algogenic behavior in rats.

Intrathecal clonidine decreases spinal nitric oxide release in a rat model of complete Freund's adjuvant induced inflammatory pain.

A long-lasting antihyperalgesic effect has been demonstrated for intrathecal (IT) clonidine, an alpha2-adrenergic agonist. In the present study, the mechanism and antihyperalgesic effects of IT clonidine were examined post-treatment in a rat model of Complete Freund's Adjuvant (CFA)-induced inflammatory hyperalgesia. Using a chronic model of spinal cord dialysis, we examined the effect of the adjuvant-induced inflammation on spinal release of nitric oxide (NO) and the development of chronic pain and assessed the antinociceptive effects and mechanisms of the alpha2-adrenergic agonist, clonidine (IT). Chronic, persistent inflammatory pain was induced by left hind paw injection of 0.3 ml CFA prepared in a mixture with Mycobacterium butyricum. Rats were randomly assigned to groups receiving IT clonidine in discrete doses of 1, 10 or 50 microg, 3 or 24 hr post-inflammation. Measurement of total NOx (NO + NO2- + NO3-) was used to determine NO release into the cerebrospinal fluid. Rat thermal antinociception was assessed using a radiant heat thermal hyperalgesia model. CFA injection resulted in significant thermal hyperalgesia throughout the four days of observation. A dose-dependent suppression of thermal hyperalgesia and spinal NO release was observed after IT clonidine treatment. Evidence from this CFA-induced inflammatory pain model suggests that clonidine's spinal antihyperalgesic mechanisms act through inhibition of spinal NO release.

The effect of third-trimester glycemic control on maternal and perinatal morbidities in pregestational diabetes mellitus.

From May 1974 to March 1989, 48 cases of pregestational diabetes mellitus treated during the third trimester of pregnancy at the Obstetric Clinic of the National Taiwan University Hospital had complete maternal-fetal chart, and were enrolled into this retrospective review. Of these cases, 28 were class B, 13 were class C and seven were class D-R. The maternal complications and perinatal morbidities of each class were reviewed. The mean fasting, postprandial plasma glucose concentrations and the mean excursion of plasma glucose levels were calculated for statistical analysis. Among the maternal complications, urinary tract infections and preterm labor were significantly associated with mean fasting plasma glucose concentrations. Among perinatal morbidities, neonatal respiratory distress and metabolic problems (including neonatal hyperbilirubinemia, symptomatic hypoglycemia, hypocalcemia and polycythemia) were significantly associated with mean plasma fasting glucose concentrations, and perinatal asphyxia was associated with a mean excursion of plasma glucose levels. In view of the paucity of knowledge about the etiology of complications in diabetic pregnancies, it is necessary to conduct a prospective multi-center study with well-characterized morbidities to search for the role of glycemic control in obstetric and perinatal complications.

Airway management and transesophageal echocardiographic monitoring for pulmonary artery sling.

Pulmonary artery sling is an uncommon vascular anomaly and can be life threatening when it causes tracheal compression. We report on a 14-day-old boy who presented with respiratory distress soon after birth. A series of examinations showed tracheal stenosis due to a pulmonary artery sling. Surgery was performed with the aid of cardiopulmonary bypass. The external compression and intrisic stenosis could not be resolved by vascular surgery because of tracheal malacia and a complete tracheal ring. We recommend cutting extra holes 1 to 2 cm from the distal end of the endotracheal tube for endobronchial intubation. The airway obstruction was resolved successfully with a custom-made endobronchial tube. However, the patient died of pneumomediastinum and pneumothorax induced by barotrauma, on the fourth postoperative day.

Failure of prevention against postoperative vomiting by ondansetron or prochlorperazine in patients undergoing gynecological laparoscopy.

BACKGROUND: Ondansetron has been approved for the treatment and prevention of postoperative emesis. Since it is presumably considered to possess potent antiemetic effect with fewer side effects, the administration of ondansetron to inhibit emesis in patients following gynecological laparoscopic surgery might be recommendable. Hence, we examined the effects of intravenous ondansetron at dosage of 4 and 8 mg in comparison with intravenous prochlorperazine at 5 mg and placebo. METHODS: A total of 120 patients were allocated randomly into 3 groups. Group 1 patients who served as control were given NaCl 0.9% 4 mL (placebo) intravenously (i.v.); patients in group 2 and group 3 were given ondansetron 4 mg ondansetron 8 mg i.v. respectively; patients in group 4 were given prochlorperazine 5 mg i.v. Premedication was omitted. RESULTS: Logistic regression analysis adjusted for prognostic factors revealed no significant difference between 5 mg prochlorperazine group and 4 mg or 8 mg ondansetron group as compared over the 24 h study period. CONCLUSIONS: The results of this study suggest that i.v. 4 or 8 mg ondansetron and 5 mg prochlorperazine were not effective in prevention of postoperative emesis in patients undergoing gynecological laparoscopy. Since the cost of ondansetron is high, its routine use for prevention against postoperative nausea and vomiting is not be recommended clinically because of its uncertain benefit.

Prevention of hypotension after spinal anesthesia for cesarean section: dextran 40 versus lactated Ringer's solution.

BACKGROUND: This study was designed to compare the efficacy of 10% dextran 40 with lactated Ringer's (LR) solution in reducing the incidence and severity of hypotension after spinal anesthesia for Cesarean section. METHODS: Sixty ASA grade I patients scheduled for Cesarean section were randomized into two groups in a double-blind fashion to receive either 500 ml of dextran 40 or 1000 ml of LR solution prior to induction of spinal anesthesia. RESULTS: The incidence of hypotension was 16 in 30 (53.3%) in the LR solution group and 8 in 30 (26.7%) in the dextran group (P < 0.05). The required dose of ephedrine for treatment of hypotension was significantly greater in the LR solution group than in the dextran group (15.5 mg versus 3.2 mg, P < 0.05). Neonatal outcome, as determined by Apgar score, was good and similar in both groups. CONCLUSIONS: We concluded that 500 ml of dextran 40 is more effective than 1000 ml of lactated Ringer's solution in reducing the incidence of hypotension induced by spinal anesthesia.

[Study of platelet aggregation affected by 8 classical recipes in rabbit].

Arachidonic acid can induce platelet aggregation in rabbits in vitro. The experimental model was designed to observe inhibitory effect of 8 classical recipes of activating blood circulation to remove the stasis on platelet aggregation in vitro. The results showed that each one of 8 classical recipes has inhibitory effect on platelet aggregation in vitro in various degree. Among them, Gexia Zhuyu Tang (GZT), Shentong Zhuyu Tang (SZT) and Shaofu Zhuyu Tang (SFZT) were more effective. The results suggested that inhibitory effect of platelet aggregation produced by 8 classical recipes might be one of mechanisms of blood stasis treatment.

Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus.

Diabetes is associated with renal calcium and magnesium wasting, but the molecular mechanisms of these defects are unknown. We measured renal calcium and magnesium handling and investigated the effects of diabetes on calcium and magnesium transporters in the thick ascending limb and distal convoluted tubule in streptozotocin (STZ)-induced diabetic rats. Rats were killed 2 weeks after inducing diabetes, gene expression of calcium and magnesium transporters in the kidney was determined by real-time polymerase chain reaction, and the abundance of protein was assessed by immunoblotting. Our results showed that diabetic rats had significant increase in the fractional excretion for calcium and magnesium (both P < 0.01), but not for sodium. Reverse transcriptase-polymerase chain reaction revealed significant increases in messenger RNA abundance of transient potential receptor (TRP) V5 (223 +/- 10%), TRPV6 (177 +/- 9%), calbindin-D28k (231 +/- 8%), and TRPM6 (165 +/- 8%) in diabetic rats. Sodium chloride cotransporter was also increased (207 +/- 10%). No change was found in paracellin-1 (cortex: 108 +/- 8%; medulla: 110 +/- 10%). Immunofluorescent studies of renal sections showed significant increase in calbindin-D28k (238 +/- 10%) and TRPV5 (211 +/- 10%), but no changes in paracellin-1 in Western blotting (cortex: 110 +/- 7%; medulla: 99 +/- 7%). Insulin administration completely corrected the hyperglycemia-associated hypercalciuria and hypermagnesiuria, and reversed the increase of calcium and magnesium transporter abundance. In conclusion, our results demonstrated increased renal calcium and magnesium transporter abundance in STZ-induced diabetic rats, which may represent a compensatory adaptation for the increased load of calcium and magnesium to the distal tubule.

Anesthetic effect of epidural anesthesia with cephalad or caudad catheterization for ankle surgery or hemorrhoidectomy.

BACKGROUND: The larger size of the first sacral nerve root has been reported to be an unfavorable factor leading to sacral sparing in epidural anesthesia. Previous studies have shown that an adequate analgesic effect of the epidural block was achieved with the catheter placement in the caudal direction. In this study, the anesthetic effect of epidural anesthesia with catheter placement of a cephalic or caudad direction was compared in ankle and hemorrhoid surgery. METHODS: Twenty-one ASA physical status I or II patients undergoing surgery for ankle fractures with epidural anesthesia were enrolled and randomized into two groups. The epidural catheter was placed either to a cephalad (AU group) or caudal (AD group) direction. Another 21 patients undergoing hemorrhoidectomy were also randomized into two groups to receive epidural anesthesia in a similar way (HU and HD groups). The onset for, duration of, and recovery time from epidural anesthesia and the incidence of analgesic request were recorded. RESULTS: No significant differences were demonstrated when age, height, weight or sex were compared between the four study groups. The onset time of the block and the incidence of intrasurgical analgesic request were lower in the caudal subgroup when the ankle surgery patients were compared. Otherwise, there were no significant differences in the duration of anesthesia and time to recovery or level of anesthesia. CONCLUSION: Injection of local anesthetic solution through a caudally oriented epidural catheter produces faster onset and superior quality of anesthesia in comparison with the injection through the cephaladly oriented catheter in ankle surgery, but not hemorrhoidectomy.