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Background: Both electrocardiogram (ECG) and heart rate variability (HRV) are hallmark markers of cardiovascular patho-physiology, and rats are readily used for understanding various cardiovascular abnormalities ailing humans. Aims: The cur-rent research has two proposals: testing the non-invasive, reusable limb electrodes made from stainless steel paper binder clip for recording rat ECG, which is like clinical clamp electrodes used for humans, and analyzing the correlation amongst HRV parameters in both rats and humans thereby evaluating whether rat and human cardiac physiology shares analogy in electrical conduction and sympathovagal modulation. Methods: Single-channel digital bipolar ECG signals (250 sam-ples/second) from rats and human subjects were recorded with the help of a two-channel Biopac amplifier and its associated software (Biopac Inc., USA). The ECG signals of rats were recorded with the laboratory-made stainless steel clip electrodes and the conventional needle electrodes. In contrast, the surface ECG was recorded from human subjects with the clinical clamp electrodes. Results: Smooth rat ECG signals with well-demarcated cliffs and troughs having patterns resembling human ECG waveforms were obtained using novel clip electrodes. In addition, the correlation amongst several HRV parameters in rats, like RR interval with heart rate and SD2 with RMSSD, agreed with the one seen in humans. Conclusion: The ECG waveform acquisitions uphold the utility of novel clip electrodes. The HRV correlation matrix heatmap of rats, when compared to humans, showcased reasonable similarity. Thus, the utility of rats as model animals and the use of ethical laboratory procedures in understanding human cardiac pathophysiology is reaffirmed.

The function of the nigro-striatal pathway on neuronal entropy in the basal ganglia (BG) output nucleus, i.e. the entopeduncular nucleus (EPN) was investigated in the unilaterally 6-hyroxydopamine (6-OHDA)-lesioned rat model of Parkinson’s disease (PD). In both control subjects and subjects with 6-OHDA lesion of dopamine (DA) the nigro-striatal pathway, a histological hallmark for parkinsonism, neuronal entropy in EPN was maximal in neurons with firing rates ranging between 15 and 25Hz. In 6-OHDA lesioned rats, neuronal entropy in the EPN was specifically higher in neurons with firing rates above 25Hz. Our data establishes that the nigro-striatal pathway controls neuronal entropy in motor circuitry and that the parkinsonian condition is associated with abnormal relationship between firing rate and neuronal entropy in BG output nuclei. The neuronal firing rates and entropy relationship provide putative relevant electrophysiological information to investigate the sensory-motor processing in normal condition and conditions such as movement disorders.

Vagus nerve stimulation (VNS) is a widely used neuromodulation technique that is currently used or being investigated as therapy for a wide array of human diseases such as epilepsy, depression, Alzheimer’s disease, tinnitus, inflammatory diseases, pain, heart failure and many others. Here, we report a pronounced decrease in brain and core temperature during VNS in freely moving rats. Two hours of rapid cycle VNS (7s on/18s off) decreased brain temperature by around $3^{\circ }$C, while standard cycle VNS (30s on/300s off) was associated with a decrease of around $1^{\circ }$C. Rectal temperature similarly decreased by more than $3^{\circ }$C during rapid cycle VNS. The hypothermic effect triggered by VNS was further associated with a vasodilation response in the tail, which reflects an active heat release mechanism. Despite previous evidence indicating an important role of the locus coeruleus-noradrenergic system in therapeutic effects of VNS, lesioning this system with the noradrenergic neurotoxin DSP-4 did not attenuate the hypothermic effect. Since body and brain temperature affect most physiological processes, this finding is of substantial importance for interpretation of several previously published VNS studies and for the future direction of research in the field.

Effects of one human-dose (30 µmol/kg) of calcium salt of diethylenetriaminepentaacetic acid (Ca-DTPA) on the urinary excretion of essential metals and on their concentration in several tissues were studied in rats by particle induced X-ray emission (PIXE). Ca-DTPA enhanced the urinary excretion of manganese, iron, copper and zinc, while their concentration in the liver, kidneys, brain and thigh bone remained unchanged. These results suggest that urinary loss of these metals caused by Ca-DTPA can be compensated by homeostatic mechanisms in the body under the treatment schedule of one human-dose per day.

Zn-DTPA was injected intraperitoneally into rats (30 µmol/kg) with a single dose or a daily dose for 10 consecutive days. Urine samples were collected for 24 hours after the single injection and tissue samples were excised 20 hours after the final of the consecutive injections. Elements in these samples were analyzed by PIXE. Zn-DTPA raised the urinary concentration of zinc and copper, and their urinary losses caused by Zn-DTPA were estimated to be 1.9 and 0.01 mg/30μmol Zn-DTPA, respectively. The concentration of metals in the liver, kidneys, brain and femurs remained unchanged. These results suggest that almost all of Zn-DTPA is excreted into the urine without replacement with other metals, and so this chelating agent may not induce any deficiencies of essential metals when animals are treated with a dose of 30 µmol/kg per day.

The relationship of liver regeneration to immunoactivity was examined after ursodesoxycholic acid (UDCA) administration to partially (about 66%) hepatectomized rats. The UDCA was given orally. Liver regeneration was evaluated by the hepatocyte mitotic index (MI) and immunoactivity by natural killer cell (NK) activity in the blood. When UDCA 12.5 mg/kg/day was administered, a significant increase in the MI was observed 2 and 3 days after hepatectomy, and the MI response 2 days after hepatectomy tended to be dose-dependent in the range of 0–25 mg/kg/day. NK activity was decreased 2 days after hepatectomy when UDCA was given, and a significant correlation between MI and NK activity was obtained. The increase in MI and decrease in NK activity was blocked completely or partially (respectively) by interleukin-2 administration. It was also noted that UDCA did not affect serum parameters indicating liver and kidney function.

These findings suggest that liver regeneration can be modified by orally administered UDCA through a change in immunoactivity.

We investigated the potential direct effects of Tokishakuyakusan (TS) on progestin [progesterone and 20 α-hydroxyprogesterone (20 α-OH-P)] and cyclic adenosine-3', 5'-monophosphate (cAMP) production in cultured rat luteal cells. In addition, we examined whether TS regulates the inhibitory effects of pituitary adenylate cyclase-activating polypeptide (PACAP), a newly found peptide, on luteinizing hormone (LH)-stimulated progesterone production. TS significantly stimulated progesterone, but not 20α-OH-P, production and cAMP accumulation through 24 hours of culture. PACAP-38 significantly elevated progesterone, 20α-OH-P and cAMP levels at all concentrations studied. On the other hand, PACAP-38 inhibited the production of progesterone and the accumulation of cAMP enhanced by LH, while the ratio of progesterone to 20α-OH-P was significantly decreased by PACAP-38 + LH. Concomitant treatment with TS and PACAP-38 + LH increased the ratio of progesterone to 20α-OH-P more than with PACAP-38 + LH. The present data have demonstrated that TS stimulates progesterone production in rat luteal cells, reconfirming our previous evidence that TS stimulates luteal steroidogenesis. The data further suggest that TS tends to attenuate PACAP's inhibition of LH-stimulated progesterone production, suggesting a luteotrophic effect within the corpus luteum.

This study investigated the effects of various concentrations and incubation time intervals of CDA-II (cell differentiation agent: a preparation of human urine) on cell viability, lipid peroxidation and glutathione and its related enzyme activities in rat hepatocytes. Based on the results of lactate dehydrogenase leakage and microscopic examination, treatment with CDA-II significantly elevated the viability of hepatocytes. The level of lipid peroxidation of cells treated with 2.5 or 5 mg/ml CDA-II was lower than the control after 4, 8 and 24 hours of incubation. Intracellular glutathione (GSH) content of cells treated with 0.25–5 mg/ml CDA-II was significantly higher than controls after 8 and 24 hours of incubation. These phenomena are beneficial to the antioxidant capabilities of hepatocytes. Furthermore, treatment of hepatocytes with CDA-II has no effect on the activities of GSH peroxidase, GSH reductase and GSH S-transferase. In conclusion, adequate concentration of CDA-II could enhance the viability and antioxidative capability of hepatocytes.

The effect of moxibustion stimulation of various skin areas (cheek, forepaw, upper arm, chest, back, lower leg, hindpaw and perineum) on cerebral blood flow (CBF) of the parietal cortex was examined in anesthetized rats after eliminating emotional influences. Moxibustion stimulation was performed by burning a moxa cone of about 4 mg weight placed on the shaved skin. CBF of the parietal cortex was measured using a laser Doppler flowmeter. Stimulation of the cheek, forepaw, upper arm and hindpaw produced significant increases in CBF, but stimulation of the other areas did not produce significant responses. Moxibustion stimulation of the forepaw and hindpaw produced an increase in the mean arterial pressure (MAP), while stimulation of the other areas did not. After spinal transection at the 2nd thoracic level, the MAP response to stimulation of the forepaw was abolished, whereas the CBF response to stimulation of the forepaw remained. The CBF response in spinalized rats was not affected by cutting cervical sympathetic and facial parasympathetic nerves, while it was almost abolished by intravenous administration of muscarinic and nicotinic cholinergic blocking agents. The CBF response was abolished by crushing the brachial plexus ipsilateral to the stimulated side. It is suggested that the increase in CBF, independent of MAP and emotional responses, elicited by moxibustion stimulation is a reflex response whose afferent pathway is composed of somatic afferent nerves, and whose efferent pathway involves intracerebral cholinergic nerves. A contribution of endogenous opioids in the present CBF responses was neglected, because naloxone did not influence the CBF responses.

This study was designed to (1) test the preventive and therapeutic effects of acupuncture on osteopenia in ovariectomized (OVX) rats, and (2) assess whether treatment of different acupuncture points causes different effects on tibiae, femora or lumbar spines. Thirty-five female Sprague-Dawley rats were divided into four groups: Sham (sham-operated, non-acupuncture); Model (OVX, non-acupuncture); Acp-A [OVX, bilateral needling of points Tsu-San-Li (ST-36) and San-Yin- Chiao (SP-6)]; and Acp-B (OVX, bilateral needling of P'i-Shu (Bl-20) and Shen Shu (Bl-23)). Operations were performed at 8 weeks of age, 1 week later the study was started and continued for 16 weeks. Ovariectomy resulted in decreased bone mineral density (BMD) compared to the sham group over time, and Acp-A tended to have higher BMD than the other OVX groups, especially for tibiae. In addition, the bone ash weight of the Acp groups tended to be heavier than the model group. Deoxypyridinoline, the urinary marker of bone resorption, also appeared to be decreased in both acupuncture groups. Similarly, microarchitecture and bone morphometry of lumbar vertebrae and tibiae, such as bone volume, trabecular thickness, trabecular number, mineralizing surface, bone formation rate, mineral apposition rate, number of nodes and number of node-terminus struts, also showed the same improvement in the acupuncture groups as compared to the model control group. Our findings showed that acupuncture may prevent the development of osteopenia in rats induced by ovariectomy. Needling of Tsu-San-Li (ST-36) and San-Yin- Chiao (SP-6) seems more effective than needling of P'i-Shu (Bl-20) and Shen Shu (Bl-23) in bone anabolic regulation.

The effects of dried Rehmanniae Radix (Di Huang) extract were investigated using a diabetic nephropathy model: rats given streptozotocin after nephrectomy. The results showed that this crude drug reduced the magnitudes of the increases in glucose, urea nitrogen, 5-hydroxymethylfurfural and thiobarbituric acid (TBA)-reactive substance levels, with the effects being most marked in the high blood glucose group. The renal histopathological lesions, which were conspicuous in rats not given dried Rehmanniae Radix extract, were ameliorated considerably in the high blood glucose group given this extract. It appears that dried Rehmanniae Radix extract may be useful as a therapeutic agent for inhibiting the progression of diabetic nephropathy. On the basis of these results, the possible mechanisms of action of this crude drug are discussed.

Nausea and vomiting are significant adverse effects of chemotherapeutic agents like cisplatin, and cause significant patient morbidity. Cisplatin treatment results in oxidant gut injury, which is postulated to be the primary cause of nausea and vomiting. We evaluated the effects of two antioxidant herbs, Scutellaria baicalensis and American ginseng berry, on cisplatin-induced nausea and vomiting using a rat model. Rats react to emetic or nausea-producing stimuli, such as cisplatin, with altered feeding habits, manifested by increased kaolin consumption (pica). We measured pica in rats to quantify cisplatin-induced nausea. We observed that pretreatment of rats with S. baicalensis or ginseng berry extracts resulted in a significant reduction in cisplatin-induced pica. The in vitro free radical scavenging ability of the herbal extract observed in the study, further confirmed the antioxidant action of the herb. We conclude that herbal antioxidants may have a role in attenuating cisplatin-induced nausea and vomiting.

Experiments were conducted to establish the safety and efficacy of Eucommia ulmoides (Du-Zhong) extract in the treatment of hypertension. Pilot experiments using rats demonstrated that E. ulmoides extract was safe to the saturation limits of the compound. The maximum tolerated dose (MTD) was 1200 mg/kg when administered by gastric gavage at a concentration of 1200 mg/ml. Also, rats given 200 mg/kg, 600 mg/kg or 1200 mg/kg doses of E. ulmoides extract daily for 28 days demonstrated no evidence of acute toxicity as determined by clinical appearance, histopathology and serum chemistry evaluation. Lastly, spontaneous hypertensive rats (SHRs) were administered E. ulmoides extract daily for 22 days. Systolic blood pressure (BP) was measured on treatment days 1, 8, 15 and 22 at 0, 1, 2 and 3 hours post-treatment. Beginning on day 8, E. ulmoides extract administered at the mid or high dosages lowered BP in male, but not female, rats. BP declined at a rate of approximately 10 mmHg per hour. The mid dosage of 600 mg/kg was found to be the minimum effective dose. In conclusion, E. ulmoides extract was non-toxic and effective in reducing systolic BP in the SHR.

Chemotherapy is highly cytotoxic, causing a number of severe adverse effects such as nausea and vomiting. Herbal medicines, which can often be used on a daily basis for prolonged treatment, may be clinically beneficial. Ganoderma lucidum or Lingzhi mushroom has been recognized as a remedy in treating a number of medical conditions, including balancing immunity and decreasing drug-induced side effects. It has been shown that rats react to emetic stimuli, like the chemotherapy agent cisplatin, by increased consumption of kaolin, known as pica; and this rat model has been utilized to evaluate novel anti-emetic compounds. In this study, we evaluated the effects of a G. lucidum extract (SunRecome^®, the most commonly used Lingzhi mushroom extract in China) in attenuating cisplatin-induced nausea and vomiting in the rat pica model. We observed that intraperitoneal cisplatin injection caused a significant increase in kaolin intake at 24, 48, 72 and 96 hours, reflecting cisplatin's nausea and vomiting action. This cisplatin-induced kaolin intake dose-dependently decreased after 1, 3 and 10 mg/kg G. lucidum extract injection (p < 0.01). In addition, there was a significant reduction of food intake after cisplatin. The cisplatin-induced food intake reduction improved significantly after G. lucidum extract administrations in a dose-related manner (p < 0.01), suggesting a supportive effect of the extract on general body condition. Future controlled clinical trials are needed to evaluate the safety and effectiveness of this herbal medication.

The aim of the present study is to probe candidate genes which were involved in the electroacupuncture (EA) analgesia and to understand the molecular basis of the individual difference of EA analgesia in rats. We compared hypothalamus transcriptional profiles of responders with those of non-responders after 1 Hz EA treatment at ST36 acupoint for 1 hour by using oligonucleotide microarray. Responders and non-responders were determined by tail flick latency (TFL). A real-time quantitative RT-PCR was applied to validate the differential expressed genes. Our study provided a global hypothalamus transcriptional profile of EA analgesia in rats. We found that 63 and 3 genes were up- and down-regulated in the responder group, respectively. Half of the differentially expressed genes were classified into 9 functional groups which were ion transport, sensory perception, synaptogenesis and synaptic transmission, signal transduction, inflammatory response, apoptosis, transcription, protein amino acid phosphorylation and G-protein signaling. Glutamatergic receptors, ghrelin precursor, melanocortin 4 receptor (MC4-R) and neuroligin 1 were found to be up-regulated in the responder group which may become new targets for nociceptive study and deserve further investigation for developing new acupuncture therapy and intervention of pain modulation.

In clinical acupuncture, when acupuncture points are stimulated, several types of reflex responses can be evoked. Consequently, different categories of physiological responses are induced, which include changes in the activities of internal organs and tissues. The acupuncture point Sanyinjiao (SP6) has been used successfully to treat different human gastrointestinal conditions. The aim of this work was to investigate the effects of end-organ response induced by acupuncture point SP6 on the bioavailability of the radiopharmaceutical sodium pertechnetate (Na^99mTcO₄) in Wistar rats. Healthy rats were allocated into 2 groups, control-CG and treated-TG. TG was bilaterally stimulated at acupuncture point SP6 with stainless steel needles. Ocular plexus administration of Na^99mTcO₄ (3.7MBq) was carried out 10 min after every needle insertion in all animals. Ten minutes later, the animals were killed, the organs were isolated, the radioactivity was determined in a well gamma counter, and the percentage of injected dose per gram of tissue (%ID/g) was determined for each organ. The %ID/g was significantly altered (p < 0.05) in the small intestine of TG (0.56 ± 0.09) when compared to CG (0.82 ± 0.18). These results may suggest that this stimulation might induce physiological responses capable of altering the bioavailability of the radiopharmaceutical sodium pertechnetate. These findings aid in providing a better understanding of acupuncture and its effects on various organs and tissues.

This study investigated the effects of the combined extracts of Ginkgo biloba, Panax ginseng, and Schizandra chinensis at different doses on hepatic antioxidant status and fibrosis in rats with carbon tetrachloride (CCl₄)-induced liver injury. Male Sprague-Dawley rats (n = 8–12 per group) were divided into the control, CCl₄, CCl₄ + silymarin (0.35%), CCl₄ + low-dose herbal extract (0.24% of Ginkgo biloba, Panax ginseng, and Schizandra chinensis extract at 1:1:1; LE), and CCl₄ + high-dose herbal extract (1.20% of the same herbal extract; HE) groups. Silymarin or herbal extract was orally given to rats a week before chronic intraperitoneal injection with CCl₄ for 6 weeks. The pathological results showed that herbal extract suppressed hepatic bile duct proliferation, and low-dose herbal extract inhibited liver fibrosis. Hepatic superoxide dismutase (SOD) activity was lower in the CCl₄ group, but there was no difference in the silymarin or herbal extract treated groups compared to the control group. Hepatic catalase activity and the ratio of reduced to oxidized glutathione were significantly higher (p < 0.05) in the HE group than those in the CCl₄ group. Silymarin and herbal extract reversed the impaired hepatic total antioxidant status (p < 0.05). Herbal extract partially reduced the elevated hepatic lipid peroxides. Hepatic transforming growth factor-β1 (TGF-β1) level decreased significantly (p < 0.05) in the LE group. Therefore, high-dose herbal extract improved hepatic antioxidant capacity through enhancing catalase activity and glutathione redox status, whereas low-dose herbal extract inhibited liver fibrosis through decreasing hepatic TGF-β1 level in rats with CCl₄-induced liver injury.

The traditional Chinese medical herb Astragalus, the dried root of Astragalus membranaceus (Fisch.) Bge., has been widely applied to treat patients with cardiovascular disease in China and has profound cardioprotective effects. This study investigated the effect of Astragalus on hemodynamic changes in adriamycin (ADR)-injured rat hearts and its underlying molecular mechanism. Sprague-Dawley rats were divided into four groups: control, ADR only, ADR + low dose of Astragalus and ADR + high dose of Astragalus. Rats were injected intraperitoneally with 6 equal doses of ADR (cumulative dose, 12 mg/kg) over a period of 2 weeks. Treatment of Astragalus began 1 day before the onset of ADR injection and was given orally once a day for 50 days (3.3 or 10 g/kg/day). Five weeks after the final injection of ADR, rats treated with ADR only showed a significant inhibition of cardiac diastolic function accompanied by the presence of ascites, a remarkable reduction in body weight and heart weight as well as survival rate compared to the controls. Moreover, SERCA2a mRNA and protein expressions in hearts were obviously downregulated by ADR. However, this impaired cardiac function was significantly improved in both doses of Astragalus feeding groups. The amount of ascites was also reduced in a similar extent in these 2 groups. Only the high dose treatment of Astragalus significantly attenuated the changes of SERCA2a expression in injured hearts and improved survival. These results indicated that Astragalus could improve cardiac function of ADR-injured rat hearts, which was partly mediated by upregulation of SERCA2a expression.

This study examined the estrogenic activity produced by aqueous extracts of silkworm (Bombyx mori) pupae in ovariectomized (OVX) rats. The components of silkworm pupae were extracted in distilled water at room temperature for 6 hours. The ovaries of six-week old female rats were then bilaterally removed. One week after OVX, the animals were treated with 200, 400 or 600 mg/kg/day of silkworm pupae extracts. The body weights of the OVX rats increased remarkably compared to the control rats, however their relative uterus weights to body weights decreased significantly. Treatment with the aqueous extracts of silkworm pupae dramatically improved the decreased uterus weights of OVX rats, with the highest increase observed in treatment with 200 mg/kg/day of the aqueous extracts. Additionally, treatment with aqueous extracts (200 mg/kg/day) of silkworm pupae significantly elevated the serum 17β-estradiol contents of OVX rats when compared to the control animals. To examine the toxic effects of silkworm pupae on the hepatic functions of OVX rats, the levels of serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) were measured. The serum GOT and GPT levels did not change in response to the administration of aqueous extracts (200, 400 and 600 mg/kg/day) for 4-weeks. Taken together, these results suggest that the aqueous extracts of silkworm pupae may have estrogenic activity, which suggests that silkworm pupae may be useful in the prevention and/or treatment of menopausal disorders caused by deficiencies in female sexual hormones, including estrogen.

The present study investigated the effects of a flavonoid extract from Cynomorium songaricum on the swimming endurance of rats by measuring changes of free radical scavenging enzymes, such as CuZn-SOD (copper, zinc-superoxide dismutase) and GSH-px (glutathione peroxidase), and body weights. Significant and dose-dependent antioxidant and anti-fatigue effects of flavonoids (rutin, catechin and isoquercitrin) on swimming rats were observed during 10 days of swimming exercise. After treatment with the flavonoid extract at doses of 0.5, 1.0, and 2.0 g/kg body weight, the CuZn-SOD and GSH-px activities in swimming rats were increased by 1.4%, 3.3%, 4.1% and 112.2%, 208.7%, 261.7%, respectively, while the levels of MDA (malondialdehyde) were decreased by 64.7%, 79.4%, and 86.4% respectively. Furthermore, the average body weight and the total swimming time were increased by 3.1%, 8.8%, 10.6%, and 7.7%, 34.5%, 61.5%, respectively. Our experimental results suggest that flavonoid supplementation could not only reduce free radical formation and scavenge free radicals, but also enhance endurance exercise performance by reducing muscle fatigue.