Severe hyponatremia and diabetes insipidus caused by low-dose cyclophosphamide in breast cancer patients: A case report and literature review.

RATIONALE: Cyclophosphamide (CTX) is widely used in the treatment of malignancies and autoimmune diseases. Although severe hyponatremia caused by low-dose CTX chemotherapy is uncommon, it can lead to serious complications and even death. PATIENT CONCERNS: A 44-year-old woman with left-sided breast cancer suddenly experienced headaches, disorientation and weakness after receiving low-dose neoadjuvant chemotherapy combined with CTX and doxorubicin. DIAGNOSES: The patient pathology showed invasive breast carcinoma. She developed severe hyponatremia and a generalized seizure after completing the first cycle of neoadjuvant chemotherapy with CTX and doxorubicin. Laboratory tests showed a serum sodium of 118 mmol/L (normal range 135-145 mmol/L) and potassium sodium 3.16 mmol/L (normal range 3.5-5.5 mmol/L). Subsequently, the patient developed secondary diabetes insipidus 4 hours after sodium supplementation, her 24-hour urine volume was 4730 mL (normal range 1000-2000 mL/24 hours), and the urine specific gravity decreased to 1.005. INTERVENTIONS: The patient was given intravenous sodium chloride (500 mL of 3%NaCl, 100 mL/hour) and potassium chloride (500 mL of 0.3%KCl, 250 mL/hour). Meanwhile, she was advised to reduce her water intake, and pituitrin was administered to prevent dehydration caused by diabetes insipidus. OUTCOMES: The patient completely recovered after correcting of the serum sodium concentration (137 mmol/L) without any neurological deficits. After discontinuing pituitrin, her 24-hour urine volume was 2060 mL and the urine specific gravity was 1.015. LESSONS: This is a typical case of severe hyponatremia induced by low-dose CTX. Clinicians and healthcare providers should be aware of this potential toxicity, and appropriate monitoring should be implemented.

A Strategy for Optimizing the Combination of Active Components Based on Chinese Medicinal Formula Sheng-Mai-San for Myocardial Ischemia.

BACKGROUND/AIMS: Traditional Chinese medicine (TCM) has been used in clinical practice for thousands of years and has accumulated considerable knowledge concerning the in vivo efficacy of targeting complicated diseases. TCM formulae are a mixture of hundreds of chemical components with multiple potential targets, essentially acting as a combination therapy of multi-component drugs. However, the obscure substances and the unclear molecular mechanisms are obstacles to their further development and internationalization. Therefore, it is necessary to develop new modern drugs based on the combination of effective components in TCM with exact clinical efficacy. In present study, we aimed to detect optimal ratio of the combination of effective components based on Sheng-Mai-San for myocardial ischemia. METHODS: On the basis of preliminary studies and references of relevant literature about Sheng-Mai-San for myocardial ischemia, we chose three representative components (ginsenoside Rb1 (G), ruscogenin (R) and schisandrin (S)) for the optimization design studies. First, the proper proportion of the combination was explored in different myocardial ischemia mice induced by isoproterenol and pituitrin based on orthogonal design. Then, the different proportion combinations were further optimized through uniform design in a multi-model and multi-index mode. Finally, the protective effect of combination was verified in three models of myocardial ischemia injured by ischemia/reperfusion, chronic intermittent hypoxia and acute infarction. RESULTS: The optimized combination GRS (G: 6 mg/kg, R: 0.75 mg/kg, S: 6 mg/kg) obtained by experimental screening exhibited a significant protective effect on myocardial ischemia injury, as evidenced by decreased myocardium infarct size, ameliorated histological features, decreased myocardial myeloperoxidase (MPO) and malondiadehyde (MDA), calcium overload, and decreased serum lactate dehydrogenase (LDH), creatine kinase MB isoenzyme (CK-MB), cardiac troponin I (cTn-I) activity. In addition, the interactions of three components in combination GRS were also investigated. The combination, compared to G, R and S, could significantly reduce the concentration of serum CK-MB and cTn-I, and decrease myocardial infarct size, which demonstrated the advantages of this combination for myocardial ischemia. CONCLUSION: Our results demonstrated that the optimized combination GRS could exert significant cardioprotection against myocardial ischemia injury with similar effect compared to Sheng Mai preparations, which might provide some pharmacological evidences for further development of new modern Chinese drug for cardiovascular diseases basing on traditional Chinese formula with affirmative therapeutic effect.

Mast cell activation in the acupoint is important for the electroacupuncture effect against pituitrin-induced bradycardia in rabbits.

This research was conducted to verify the structural and functional characteristics of mast cells in the electroacupuncture (EA) effects on bradycardia. First, we examined the mast cell density at PC 6, adjacent acupoint LU 7, and a non-acupoint. We tested the effects of EA at PC 6 on heart rate (HR) and blood pressure (BP) in rabbits with pituitrin-induced bradycardia. We also injected sodium cromolyn (Cro), a mast cell membrane stabilizer, at PC 6 30 min before EA to investigate if it affected the EA effects. The results showed that in both PC 6 and LU 7, the mast cell densities were higher than in the non-acupoint (P < 0.05). EA could induce mast cell degranulation at PC 6, which could be suppressed by sodium cromolyn (P < 0.05). EA improved HR, though the change was relatively small in the initial stage with a significant change at 35 min after modelling (P < 0.05). BP significantly improved at 10 min after the onset of pituitrin-induced bradycardia (P < 0.05). The EA effects on both HR and BP were suppressed by sodium cromolyn (P < 0.05). Therefore, we concluded that mast cells in the acupoint are important for the EA effects against pituitrin-induced bradycardia in rabbits.

Protective effects of Shexiang Tongxin Dropping Pill on pituitrin­induced acute myocardial ischemia in rats.

Shexiang Tongxin Dropping Pill (STP) is an established traditional Chinese medicine that is widely used for the treatment of ischemic heart disease (IHD), although its mechanisms remain unclear. The present study investigated the protective effects of STP following pituitrin (PTT)­induced myocardial ischemia in rats. ST­segment elevation, blood rheology, and the serum levels of creatine kinase­MB (CK­MB) and lactate dehydrogenase (LDH) were measured. Following heart excision, histological analysis using hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP nick end labeling were performed. The mRNA expression levels of B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein (Bax) were determined using reverse transcription­quantitative polymerase chain reaction, and their protein expression was detected using immunohistochemistry. The results demonstrated that STP treatment protected against ST elevation, lowered whole blood viscosity, and reduced the serum levels of CK­MB and LDH following acute myocardial ischemia. In addition, STP treatment restored the histopathological change following PTT­induced myocardial ischemia, and resulted in downregulated expression of Bax and upregulated expression of Bcl­2 in myocardial tissue. The present study demonstrates the cardioprotective ability of STP in a rat model of myocardial ischemic injury, which may be attributed to its anti­apoptotic properties. The cardioprotective properties of STP require further investigation to determine whether it may be used for the clinical treatment of IHDs.

[The natural peptide geroprotector antiarhythmic action].

The research of biological activity of peptide geroprotector Slavinorm on the basis of calf aorta extract was conducted in experimental models of hypertension and chloride-calcium arrhythmia. The research results showed that in experimental model of arrhythmia in rats induced by pituitrin administration, intraventricular and intramuscular introduction of Slavinorm in therapeutical dose had caused to leveling of hypertension symptoms. That was expressed in normalization of blood pressure characteristics, body weight, heart and kidney weight. In the experimental model of chloride-calcium arrhythmia in rats inrtaventricular and intramuscular introduction of Slavinorm showed the ability to predict the arrhythmia development caused by the Calcium Chloride administration. The research results testify to availability of the medication research in the capacity of the medication for treatment of age related pathology conditioned by vessels impaired function.

Diminished gray matter within the hypothalamus in autism disorder: a potential link to hormonal effects?

BACKGROUND: Subjects with autism suffer from impairments of social interaction, deviations in language usage, as well as restricted and stereotyped patterns of behavior. These characteristics are found irrespective of age, IQ, and gender of affected subjects. However, brain changes due to age, IQ, and gender might pose potential confounds in autism neuroimaging analyses. METHODS: To investigate gray matter differences in autism that are not related to these potential confounds, we performed a voxel-based morphometry analysis in 52 affected children and adolescents and 52 matched control subjects. RESULTS: We observed diminished gray matter in a region of the hypothalamus, which synthesizes the behaviorally relevant hormones oxytocin and arginine vasopressin. CONCLUSIONS: This finding provides support for further investigations of the theory of abnormal functioning of this hormonal system in autism and potentially for experimental therapeutic approaches with oxytocin and related neuropeptides.

Anti-hypoxia activity and related components of Rhodobryum giganteum par.

Different extracts of Rhodobryum giganteum Par. were screened with mice model of acute myocardial hypoxia induced by isoproterenol and pituitrin, eight compounds, i.e. p-hydroxycinnamic acid, caffeic acid-4-O-ß-d-glucopyranoside, salicin, 7,8-dihydroxy coumarin, menthol, allantoin, palmitic acid, palmitamide were isolated and identified from the active fraction, among which p-hydroxycinnamic acid and 7,8-dihydroxy coumarin were confirmed having protective effects on myocardial hypoxia-reoxygenation injury, suggesting that these two components were major active ingredients of R. giganteum for cardiovascular disease.

Centrally administered ascorbic acid induces antidiuresis, natriuresis and neurohypophyseal hormone release in rats.

OBJECTIVE: Ascorbic acid represents one of the most important antioxidants and neuromodulators, and plays an important role in the cerebral system. In the present study, we investigated the central effect of ascorbic acid on fluid regulation and electrolyte homeostasis. METHODS: Male Wistar rats were implanted with stainless steel cannulas into the lateral ventricle, and sodiun excretion and urinary volume were measured after intracerebroventricular (i.c.v.) injection of ascorbic acid (200 or 600 nmol/rat). In another set of experiments, vasopressin and oxytocin plasma levels were evaluated 10, 20 and 30 minutes after ascorbic acid i.c.v. injection. RESULTS: The administration of ascorbic acid to conscious rats resulted in a significant decrease in urinary volume and an increase in the renal excretion of sodium, with a concomitant increase in the plasma levels of vasopressin and oxytocin. CONCLUSIONS: These results suggest that ascorbic acid may play a significant role in the central regulation of fluid and electrolyte homeostasis.

[Optimization of PNS/TGCO components effect on experimental Qi stagnation and blood stasis type of coronary heart disease with increase-decrease baseline geometric proportion design method].

OBJECTIVE: Preliminary exploration of Panax notoginseng saponins (PNS) and total saponins from Cornus officinalis (TGCO) components treatment and characteristics of Qi stagnation and blood stasis type of coronary heart disease. METHODS: With increase-decrease baseline geometric proportion design method to Optimization of PNS/TGCO components, through observing different proportions effective components effect on mice with pituitrin-induced acute myocardial ischemia and the time of hypoxia tolerance. RESULTS: Prescriptions 1, 2, 3 and Xuesaitong groups had a certain degree of improvement the role of myocardial ischemia and prescriptions 4, 5, 6, compared with the control group with no significant changes; Prescriptions 3, 4, 5, 6 had a certain role in anti-anoxia in mice, prescriptions 1, 2 and Xuesaitong group, together with the control group with no significant changes. CONCLUSION: Prescription 3 has some effect on improving the role of myocardial ischemia and has a certain role in anti-anoxia. It's the best ratio of PNS/TGCO components for the treatment of Qi stagnation and blood stasis type of coronary heart disease.

[Effect of infrared laser on pituitrin-induced bradycardia in rabbits].

OBJECTIVE: To observe the effect of infrared laser stimulation on Neiguan (PC 6) for bradycardia of rabbits induced by injection of pituitrin. METHODS: 10.6 microm CO(2) infrared laser, 650 nm semiconductor red laser and the compound laser of their aggregation were sent out by a compound laser sanatory instrument to stimulate Neiguan (PC 6) respectively for the purpose of analyzing the differences of the effects exerted by infrared laser and red laser as well as the changes of the effects after their aggregation. RESULTS: After 30 min and 40 min of the injection of pituitrin, the heart rate showed no significant difference between 10.6 microm CO(2) infrared laser group and the normal control group (P>0.05). However, the heart rate showed significant difference between the 650 nm semiconductor red laser group and the normal control group (P<0.05). After 30 min of the injection of pituitrin, the heart rate of the compound laser group were significantly different to that of the untreated group (P<0.05), and it was not significantly different to that of the normal control group (P>0.05). However, the heart rate of non-acupoint stimulated by the compound laser group showed no significant difference to that of the untreated group (P>0.05), and it was significantly different to that of the normal control group (P<0.05). CONCLUSION: Stimulation on Neiguan with 10.6 microm CO(2) infrared laser can evidently improve the bradycardia induced by injection of pituitrin, while the 650 nm semiconductor red laser has no such function, but they have coordinating effect. The thermal effect produced by CO(2) infrared laser stimulating acupoint is probably beneficial for semiconductor laser penetrating skin as well as the biochemical reactions it carries. The improvement of heart rate produced by the laser stimulation on Neiguan (PC 6) has relative specificity.

Effect of different LLLT on pituitrin-induced bradycardia in the rabbit.

The objective of this paper was to observe the effect of low-level combined- or single-laser irradiation on bradycardia produced by pituitrin in rabbits. A combined-laser apparatus was made. A 10.6-microm CO2 laser and a 650-nm semiconductor laser, transmitted by different optical fibers, converged to output and irradiate on the Neiguan (PC6) acupuncture point in rabbits with bradycardia produced by pituitrin. Thirty minutes after the model was set, the heart rates of the combined-laser Neiguan group made quicker recoveries than those of the model control group, the laser-control group, or the single-laser Neiguan group (P<0.05), and the heart rates of the single-CO2-laser Neiguan group were similar to those of the normal group (P>0.05). However, there were significant differences between the 650-nm-laser Neiguan group and the normal control group (P<0.05). The combined-laser irradiation certainly has a curative effect on bradycardia produced by pituitrin. A single CO2 laser could accelerate the recovery from bradycardia, while single 650-nm-laser irradiation on the Neiguan acupoint does not produce such an effect.

Identification of a novel receptor for an invertebrate oxytocin/vasopressin superfamily peptide: molecular and functional evolution of the oxytocin/vasopressin superfamily.

Annetocin is structurally related to an OT (oxytocin)/VP (vasopressin) family peptide, which has been isolated from the earthworm Eisenia foetida and has been shown to induce OT-like egg-laying behaviour. We now report the identification of an endogenous AnR (annetocin receptor). The deduced AnR precursor displays high sequence similarity with OT/VP receptors. Genomic analysis of the AnR gene revealed that the intron-inserted position is conserved between the AnR gene and the mammalian OT/VP receptor genes. These results indicate that AnR and mammalian OT/VP receptors share a common ancestor gene. Administration of annetocin to the AnR expressed in Xenopus oocytes induced a calcium-dependent signal transduction. Reverse transcriptase-PCR analysis and in situ hybridization showed that the AnR gene is expressed specifically in the nephridia located in the clitellum region, although the nephridia are distributed throughout the worm body. This result suggests that annetocin induces egg-laying behaviour through its action on the nephridia. This is the first description concerning the functional correlation between an invertebrate OT/VP-related peptide and egg-laying behaviour.

[Study on free radical mechanism of guanxin II in antagonizing ischemic myocardial damage].

OBJECTIVE: To study comparatively the effect of Guanxin II and its constituents, including Salvia, Red Peony root, Chuanxiong, Safflower and Dalbergia wood, in scavenging active oxygen free radical (OFR) to explore their mechanism in overcoming the experimental acute ischemic myocardial injury and protecting myocardial tissue. METHODS: The experimental acute myocardial ischemic model was established by intraperitoneal injection of pituitrin to rats. OFR level in animal heart tissue was directly measured with low-temperature electron paramagnetic resonance (EPR) spectrometer. RESULTS: The pathological examination of HE stained slide of myocardial tissue and electrocardiography of model animal showed that typical changes of acute myocardial ischemia occurred in myocardial tissue, EPR showed that OFR level in myocardial tissue increased abnormally. The ethanol extract of Guanxin II and its constituents could lower the increased OFR level close to normal, thus to alleviate the myocardial damage. CONCLUSION: Overproduction of OFR could induce damage of heart tissue, its level could be measured directly using low temperature EPR. One of the molecular mechanisms of Guanxin II and its constituents in antagonizing and repairing myocardial damage is to scavenge the abnormal increased active OFR in tissue. This study has provided a basis for further studying the mechanism of Chinese composite recipes and their constituents.

[Effect of ginsenoside Rg2 on chemical myocardial ischemia in rats].

OBJECTIVE: To investigate the protective effect of Ginsenoside Rg2 on Chemical myocardial ischemia. METHOD: The models of myocardial ischemia were built in rats with isoproterenol, sodium nitrite,pituitrin. Ginsenoside Rg2 (iv 2.5, 5.0, 10.0 mg x kg(-1)) were intravenously administered. RESULT: Ginsenoside Rg2 could improve the abnormal electrocardiogram (ECG), reduce the arca of myocardial ischemia and improve the abnormal zymologic value of myocardial. CONCLUSION: Ginsenoside Rg2 has inhibitory function on myocardialischemia.

Study on free radical mechanism of guanxin II in antagonizing ischemic myocardial damage / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study comparatively the effect of Guanxin II and its constituents, including Salvia, Red Peony root, Chuanxiong, Safflower and Dalbergia wood, in scavenging active oxygen free radical (OFR) to explore their mechanism in overcoming the experimental acute ischemic myocardial injury and protecting myocardial tissue.</p><p><b>METHODS</b>The experimental acute myocardial ischemic model was established by intraperitoneal injection of pituitrin to rats. OFR level in animal heart tissue was directly measured with low-temperature electron paramagnetic resonance (EPR) spectrometer.</p><p><b>RESULTS</b>The pathological examination of HE stained slide of myocardial tissue and electrocardiography of model animal showed that typical changes of acute myocardial ischemia occurred in myocardial tissue, EPR showed that OFR level in myocardial tissue increased abnormally. The ethanol extract of Guanxin II and its constituents could lower the increased OFR level close to normal, thus to alleviate the myocardial damage.</p><p><b>CONCLUSION</b>Overproduction of OFR could induce damage of heart tissue, its level could be measured directly using low temperature EPR. One of the molecular mechanisms of Guanxin II and its constituents in antagonizing and repairing myocardial damage is to scavenge the abnormal increased active OFR in tissue. This study has provided a basis for further studying the mechanism of Chinese composite recipes and their constituents.</p>

Effect of ginsenoside Rg2 on chemical myocardial ischemia in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of Ginsenoside Rg2 on Chemical myocardial ischemia.</p><p><b>METHOD</b>The models of myocardial ischemia were built in rats with isoproterenol, sodium nitrite,pituitrin. Ginsenoside Rg2 (iv 2.5, 5.0, 10.0 mg x kg(-1)) were intravenously administered.</p><p><b>RESULT</b>Ginsenoside Rg2 could improve the abnormal electrocardiogram (ECG), reduce the arca of myocardial ischemia and improve the abnormal zymologic value of myocardial.</p><p><b>CONCLUSION</b>Ginsenoside Rg2 has inhibitory function on myocardialischemia.</p>

The effects of electroacupuncture at the heart meridian on myocardial contractile function in rabbits with myocardial ischemia.

Acute myocardial ischemia was induced by intravenous injection of pituitrin, and electroacupuncture (EA) was applied at the Heart and Lung Meridians (HM and LM), 3 points on each meridian. The changes in the left intraventricular pressure (LVP), the maximum rise rate of intraventricular pressure (LVP dp/dtmax), the area of cardiac force loop (ACFL), and the maximum shortening velocity of myocardial contractile element (Vmax) were observed. As a result, there were significant differences in the improvement of LVP, LVP dp/dtmax, ACFL and Vmax between EA at HM and LM. The regulatory action of EA at HM on the myocardial contractile function was significantly better than that of EA at LM, indicating that HM has a close relationship with the myocardial contractile function.

The effect of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and its metabolites on neurohypophysial hormone release from the isolated rat hypothalamus.

Methylenedioxymethamphetamine (MDMA, 'ecstasy'), widely used as a recreational drug, can produce hyponatraemia. The possibility that this could result from stimulation of vasopressin by MDMA or one of its metabolites has been investigated in vitro. Release of both oxytocin and vasopressin from isolated hypothalami obtained from male Wistar rats was determined under basal conditions and following potassium (40 mM) stimulation. The results were compared with those obtained for basal and stimulated release in the presence of MDMA or metabolites in the dose range 1 microM to 100 pM (n=5 - 8) using Student's t-test with Dunnett's correction for multiple comparisons. All compounds tested affected neurohypophysial hormone release, HMMA (4-hydroxy-3-methoxymethamphetamine) and DHA (3,4-dihydroxyamphetamine) being more active than MDMA, and DHMA (3,4-dihydroxymethamphetamine) being the least active. The effect on vasopressin release was greater than that on oxytocin. In the presence of HMMA the ratio test:control for basal release increased for vasopressin from 1.1+/-0.16 to 2.7+/-0.44 (s.e.m., P<0.05) at 10 nM and for oxytocin from 1.0+/-0.05 to 1.6+/-0.12 in the same hypothalami. For MDMA the ratio increased to 1.5+/-0.27 for vasopressin and to 1.28+/-0.04 for oxytocin for 10 nM. MDMA and its metabolites can stimulate both oxytocin and vasopressin release in vitro, the response being dose dependent for each drug with HMMA being the most potent.

[Experimental study on effect of sini decoction on myocardial endothelin in myocardial ischemic rats].

OBJECTIVE: To study the molecular mechanism of effect of Sini Decoction (SND) on myocardial endothelin (MET) in myocardial ischemic rats. METHODS: Sprague-Dawley rats were randomly divided into 3 groups, the normal control group, the ischemia group and the SND group. Myocardial ischemia was produced by pituitrin in the latter two groups. The content, immunohistochemical assay and gene expression of MET-1 were determined in all the three groups and compared. RESULTS: The content of MET in the SND group was significantly lower than that in the ischemia group (P < 0.01). Immunohistochemical examination showed that MET-1 was mainly located at the cardiac muscle cells and vascular endothelial cells with the grey scale obviously lower in the ischemia group than that in the control group and the SND group (P < 0.01). While RT-PCR showed that the grey scale of PCR product band in the ischemia group was significantly higher than that in the other two groups (P < 0.01). CONCLUSION: SND could significantly lower MET content, it may be related to the effect of SND in inhibiting MET-1 gene expression and protein synthesis.