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PubMed1982

Cimetidine effect of dopaminergic modulation of prolactin release in healthy women.

The aim of the present study was to test whether cimetidine (Cim) influences PIF (prolactin inhibitory factor), and thereby indirectly affects the release of prolactin (PRL) from the pituitary lactotrophs. For that purpose 10 mg metoclopramide (Met), known for its dopamine-receptor blocking properties, were first given orally to 6 subjects. This raised the PRL level from 13 +/- 2 to 97 +/- 12 ng/ml in 60 min (p less than 0.001). PRL tended to plateau at this level until 120 min. An additional 7 subjects were then injected iv with 400 mg Cim, 90 min after oral administration of placebo. Placebo did not change the basal PRL level, but the subsequent Cim injection raised the PRL level from 14 +/- 4 to 66 +/- 9 ng/ml (p less than 0.01). When, in the same subjects, an oral dose of Met was given (10 mg) PRL increased from 19 +/- 4 to 112 +/- 10 ng/ml (p less than 0.001). A subsequent Cim injection, given on top of the PRL plateau, 90 min after the Met ingestion, however, failed to induce any further increase in PRL. To exclude that this failure was not merely a reflection of a Met-induced depletion of the PRL stores, 25 micrograms thyrotropin-releasing hormone (TRH) were given iv to an additional 6 subjects, 90 min after ingestion of either placebo or Met. Also in these subjects placebo left basal PRL unaffected. The subsequent TRH injection, however, raised PRL from 10 +/- 2 to 55 +/- 6 ng/ml (p less than 0.001). Met increased PRL from 17 +/- 4 to 133 +/- 19 ng/ml (p less than 0.01) in these subjects, and TRH, subsequently injected, induced a further PRL increase to 174 +/- 18 ng/ml (p less than 0.01). The observation that Cim fails to elicit an increase in PRL after priming with Met thus indicates that Cim, under normal conditions, stimulates the PRL release via a reduced dopaminergic inhibition of the lactotrophs.

Adolescent↗
PubMed1999

Chronic clomipramine administration reverses NMDA-evoked decreases in dopamine release in the raphe nuclei.

The effect of acute or chronic treatment with the antidepressant clomipramine (CIM) on basal and N-methyl-d-aspartate (NMDA) evoked release of dopamine (DA) in rat raphe has been studied using microdialysis. Acute injection of CIM (10 or 20 mg/kg) caused a decrease in raphe DA release, as did infusion of NMDA (25-100 microM) into this region. When NMDA infusion was preceded by a single acute injection of CIM no differences between NMDA and NMDA plus CIM treated groups was observed. Chronic (15 day) treatment with CIM caused a dose-dependent increase in basal extracellular DA. In addition the effect of infusing NMDA into the raphe on DA release was markedly reduced or abolished. This suggests that adaptive changes occur in NMDA receptor function during treatment with CIM.

Animals↗
PubMed2003

Coxsackievirus B1-induced chronic inflammatory myopathy: differences in induction of autoantibodies to muscle and nuclear antigens by cloned myopathic and amyopathic viruses.

Infection of susceptible strains of mice with the myopathic Tucson strain of coxsackievirus B1 (CVB1(T)) leads to the development of chronic inflammatory myopathy (CIM). The underlying mechanism of CIM appears to be immunopathic, but it is not known whether autoimmunity is involved. The objectives of this study were to determine whether autoantibodies are produced and whether they correlate with the pathology of CIM. Mice were infected with either a myopathic (MP1.23 or MP1.24) or an amyopathic (AMP2.17) CVB1(T) cloned virus. The two myopathic (MP) viruses cause CIM, whereas the amyopathic (AMP) virus, derived from a variant of the same parent, causes the same acute disease but does not cause CIM. Antimuscle IgG was found in 51% of MP1.23-infected and 58% of MP1.24-infected mice but in just 18% of mice infected with AMP2.17 and in 10% of controls (MP vs AMP: chi(2), P < or =.006). Several staining patterns were observed, indicating that autoantibodies of multiple specificities were produced. Antinuclear antibodies were found in 57% of MP1.23-infected and 27% of MP1.24-infected mice but were rare in mice infected with AMP2.17 (0%) or in controls (4%) (MP vs AMP: chi(2), P < or =.01). Antiviral-antibody titers were higher with MP virus than with AMP virus (ANOVA, P <.001). A trend toward an association between antiviral antibody or autoantibodies and the presence or severity of clinical measures of CIM was noted but was not significant. These data suggest that the autoantibodies do not mediate muscle disease but are an independent manifestation of an immunopathic response induced by infection with MP but not AMP CVB1(T).

Animals↗
PubMed2004

[The consulting of internal medicine in primare care improves the efficacy of medical care].

BACKGROUND AND OBJECTIVE: Our aim was to evaluate the efficacy of the consulting of internal medicine (CIM) in primary care (PC) on the resolution of medical processes. PATIENTS AND METHOD: Prospective case-control study of a population of 87,016 inhabitants during a 1-year period. Patients (2,167) jointly attended by family physicians (FP) and consulting internists (CI) who go weekly to the primary care center (PCC) to attend patients who otherwise would have been referred to specialized consultation (SC). As the control group 1,470 patients were randomly and simultaneously chosen among the total of 14.687 first medical referrals during the period of the study. RESULTS: We observed a significant reduction in: referrals to SC (22%; CI 95%, 18-26%); mean time for SC (23.6 days; CI 95%, 17.3-29.9 days); mean number of tests per patient ordered by FP (0.53; CI 95%, 0.31-0.75) or by CIM (1.22; CI 95%, 1.02-1.40); mean time for patient information on those tests ordered by CIM (21.2 days; CI 95%, 8.5-33.9 days); mean time for the resolution of processes (39.4 days; CI 95%, 35.5-43.3 days); crossed SC rate (23.7%; CI 95%, 20.3-27.1%); and specialized follow-up visits (28.8%; CI 95%, 24.5-33.1%) (p < 0.005 in all cases). The resolution rate of processes (15%; CI 95%, 11-19%) and the discharge rate (41.6%; CI 95%, 35.5-47.7%) were significantly higher for the CIM (p < 0.01 in both cases). The referral rate to SC showed a negative correlation (r = 0.81; p < 0.01) with the management quality, and it related to type of training, age and years of medical practice of the general practitioner (GP). The satisfaction of patients and GPs with the CIM was very high. CONCLUSIONS: CIM in PC improves the efficacy of specialized outpatient medical care.

Adolescent↗
PubMed2002

Physicochemical properties of amorphous salt of cimetidine and diflunisal system.

The purpose of this study was to prepare amorphous precipitates of the binary system of cimetidine (CIM) and diflunisal (DIF) and to investigate the physicochemical properties of the precipitates. To achieve this, the interaction between CIM and DIF molecules was studied by means of nuclear magnetic resonance (NMR) and Fourier-transform infrared (FTIR) measurements. The binary system of CIM and DIF was found to become amorphous upon precipitation from ethanol solution, without heating or melting. In the thermal analysis by TG-DTA equipped with a mass spectrometer, decarboxylation of DIF was found to occur below its melting temperature. In NMR studies, the chemical shifts of a proton in the imidazole ring of CIM and the carbon to which the DIF carboxyl group is bound were found to change depending on the composition of the binary system. The change in NMR chemical shifts suggested that a salt was formed between CIM and DIF. The precipitates had higher solubility than intact drugs due to this salt formation. The results suggest that CIM may be useful as an amorphous carrier, without requiring heating or melting, due to the formation of a salt with acidic drugs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

In vitro taurine uptake into cell culture influenced by using media with or without CO2.

Buffers used to incubate cells for pharmacological or toxicological studies are usually of very simple composition, far from the composition of biological fluids or cell culture media. Comparative studies on taurine uptake levels by cultured cells show that a new CO2-Independent Medium (CIM) is suitable for incubating cells in place of the Krebs-Ringer buffer (KR) usually used. Basal uptake level of taurine was lower for cells incubated in CIM or in other culture media when compared to those incubated whether in KR or in other "physiological buffers." Isoproterenol depressed similarly the taurine uptake in cells incubated in CIM or KR. The same uptake modulation by beta-alanine, GES, GABA, or HEPES was observed for cells incubated in CIM or KR. C6 cells growth in CIM was dependent on the starting cell density when classically vented T-flasks were used, growth being notably reduced at low density. In tightly closed flasks cells grew in CIM similarly to control cultures maintained in M199 medium or DMEM.

Adrenergic beta-Agonists↗
PubMed2006

A treatment model for craving identification and management.

This article presents an addiction treatment model based on craving identification and management (CIM). Craving is broadly defined as the desire to use alcohol or other drugs; it increases the likelihood of use of these substances. In the CIM Model treatment interventions are referenced to craving, i.e., helping clients to identify their craving level and equipping them with strategies to avoid use. Four causes of craving are identified: (1) environmental cues (triggers): exposure to people, places, and things associated with prior drug-using experiences may cause immediate and overwhelming craving; (2) stress: addicted persons experience stress as craving; (3) mental illness; and (4) drug withdrawal: symptoms of both mental illness and withdrawal lead to craving if clients associate use with relief of these symptoms. The CIM Model incorporates four service delivery elements: Relapse Prevention Workshop, individual counseling, medical/psychiatric services, and screening for ongoing drug use. At its core, the CIM Model asks clients to be aware of craving, analyze its causes, and, based on those causes, implement specific strategies to prevent and manage craving. The CIM Model combines several treatment components, including control of exposure to environmental cues, establishment of a daily schedule, the use of behaviors that dissipate craving (tools), and treatment (with medications when appropriate) of mental health and withdrawal symptoms. The CIM Model is a client-derived approach to achieving and maintaining sobriety based on a process of analyzing craving and managing it with an individualized program of recovery activities.

Behavior, Addictive↗
PubMed2006

Correlative imaging strategies implementing CT, MRI, and PET for staging of childhood Hodgkin disease.

BACKGROUND: The value of different correlative imaging strategies with F18-fluorodeoxyglucose positron emission tomography (FDG-PET) and conventional imaging modalities (CIM) for initial staging of pediatric Hodgkin disease (HD) was assessed. METHODS: Thirty-three patients (age, 4 to 18 y) with histologically proven HD underwent initial staging with computed tomography (thorax), magnetic resonance imaging (neck, abdomen, pelvis), and FDG-PET in a prospective study. Image fusion (PET-CIM) was performed using a semiautomatic voxel-based algorithm. Analysis of separate, side-by-side (SBS) and fused PET and CIM was performed evaluating 21 nodal and 6 extranodal regions per patient for presence of lymphoma, applying a 5-point confidence scale. The reference data was clinical follow-up (>12 mo). RESULTS: Concerning lymph node regions above and below the diaphragm the accuracy of CIM, PET, SBS, and image fusion was 86%, 89%, 94%, 97%, and 94%, 94%, 97%, 98%. In extranodal regions, the accuracy was 96%, 96%, 100%, and 100%. The reviewers' confidence was improved significantly by image fusion. Staging and therapy assignment on the basis of CIM was correctly modified by SBS in 5 and 4, by image fusion in 7 and 5 patients. CONCLUSIONS: Combined reading of FDG-PET and CIM is crucial for accurate staging in pediatric HD. Image fusion improves the observers' confidence and has impact on the therapeutic management.

Adolescent↗
PubMed2002

Intestinal metaplasia of the gastric cardia: A prospective study with enhanced magnification endoscopy.

OBJECTIVE: There are no endoscopic features that distinguish intestinal metaplasia of the cardia (CIM) from the normal cardia. Biopsy specimens are therefore randomly obtained from normal-appearing mucosa with significant potential sampling errors. Enhanced magnification endoscopy involves the combined use of magnification endoscopy with acetic acid instillation. This study assessed the value of enhanced magnification endoscopy in detecting CIM. METHODS: Patients undergoing elective upper endoscopy were invited to participate in the study. Patients were included if the squamocolumnar junction and the esophagogastric junction were judged to be at the same level. Enhanced magnification endoscopy was performed with 3% acetic acid instillation. Standard endoscopy was followed by magnification endoscopy and repeated after acetic acid spraying. Surface patterns were characterized before and after acetic acid spraying. The observed surface patterns were compared with histological results obtained from a single targeted biopsy specimen of each pattern. RESULTS: The overall prevalence of CIM was 34.8% (86/247 patients). After excluding 52 patients because of endoscopic evidence of Barrett's esophagus, 195 patients were eligible for participation in the study. In the study group, CIM was detected in 86 patients (44.1%) in targeted biopsy samples. No dysplasia was identified. Enhanced magnification endoscopy detected four different patterns of the mucosal surface: I) round pits, II) reticular, III) villous, and IV) ridged. The yields of detection of intestinal metaplasia according to endoscopic patterns were I) 0%, II) 5.3% (odds ratio = 0.05), III) 57.7% (odds ratio = 7.5, p = 0.0001), and IV) 95.8% (odds ratio = 42.8, p = 0.0001). CONCLUSIONS: CIM is more common than previously reported. Enhanced magnification endoscopy identifies two characteristic endoscopic patterns, villous (pattern III) and ridged (pattern IV), with outstanding clarity and resolution that correlate with histological identification of CIM with a single targeted biopsy sample. Enhanced magnification endoscopy will permit longitudinal studies of an entity that can be identified endoscopically.

Acetic Acid↗
PubMed1987

A comparison of the inhibitory effects of roxatidine acetate hydrochloride and cimetidine on cytochrome P-450-mediated drug-metabolism in mouse hepatic microsomes and in man in vivo.

The inhibitory effects of roxatidine acetate hydrochloride (ROX), a new H2-receptor antagonist, on the oxidative drug-metabolizing enzyme system in mouse hepatic microsomes and in man in vivo were compared with those of cimetidine (CIM). CIM markedly inhibited testosterone 6 beta-, 7 alpha- and 16 alpha-hydroxylase, aminopyrine N-demethylase and aniline hydroxylase activities in mouse hepatic microsomes with inhibition constants (Ki) of 0.2-3.49 mM. ROX exhibited much weaker inhibitory effects on each enzyme activity with 12 to 100-fold higher values of Ki than those of CIM. CIM gave type II difference spectra with dissociation constants (Ks) of 10.4 and 111 microM while ROX gave reverse type I difference spectra with Ks of 55.6 microM. The ratio of 6 beta-hydroxycortisol (6 beta-OHF) to 17-hydroxy corticosteroids (17-OHCS) in urine, used as an indicator of oxidative drug-metabolizing capacity in man, was decreased by 25-35% of the original level on 1-3 d after oral treatment with 800 mg/d of CIM. The ratio was not significantly changed during oral treatment with 150 mg/d of ROX. These results indicate that ROX exhibits a lower affinity for cytochrome P-450 and a lower inhibitory potency on the drug-metabolizing enzymes in hepatic microsomes than does CIM.

Aminopyrine N-Demethylase↗
PubMed1994

The effect of cimaterol on muscle fiber characteristics, capillary supply, and metabolic potentials of longissimus and semitendinosus muscles from young Friesian bulls.

The objective of this study was to determine the effect of the beta-adrenergic agonist cimaterol (CIM) on fiber characteristics, capillary supply, and metabolic enzyme activities in muscles of young Friesian bulls. Four pairs of monozygotic twins in each of three live weight groups (WG) were used (initial average live weight [LW]: 162, 299, and 407 kg, respectively). Within each pair, one twin was fed .06 mg of CIM.kg LW-1.d-1 for 90 d. The other twin served as control (C). Needle biopsies were obtained from the longissimus (LM) and semitendinosus (ST) muscles at d 82 to 84 of treatment, and muscle fibers were identified as slow-twitch (Type I) or fast-twitch (Type IIA or Type IIB) by the myosin ATPase stain. In LM, the proportion of Type I (C: 24.0%, CIM: 20.4%; P < .07) and Type IIA fibers (C: 24.2%, CIM: 8.6%; P < .001) decreased, whereas the proportion of Type IIB fibers increased (C: 51.7%, CIM: 71.1%; P < .001). Cimaterol increased the cross-sectional area of Type I (P < .02) and Type IIB fibers (P < .001), with no change in Type IIA fibers. Overall, the mean fiber area increased (C: 2,363 microns 2, CIM: 3,934 microns 2; P < .001). The number of capillaries per fiber did not change, but the number of capillaries per square millimeter decreased (P < .001) after CIM treatment. Cimaterol changed metabolic enzyme activities toward lower oxidative capacity of the muscle (lactate dehydrogenase: +22%, hydroxyacyl-CoA dehydrogenase: -33%, and citrate synthetase: -34%; all P < .001) and reduced the glycogen content by 25% (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2005

Distinction between short-segment Barrett's esophageal and cardiac intestinal metaplasia.

AIM: To investigate the roles of mucin histochemistry, cytokeratin 7/20 (CK7/20) immunoreactivity, clinical characteristics and endoscopy to distinguish short-segment Barrett's esophageal (SSBE) from cardiac intestinal metaplasia (CIM). METHODS: High iron diamine/Alcian blue (HID/AB) mucin-histochemical staining and immunohistochemical staining were used to classify intestinal metaplasia (IM) and to determine CK7/20 immunoreactivity pattern in SSBE and CIM, respectively, and these results were compared with endoscopical diagnosis and the positive rate of gastroesophageal reflux disease (GERD) symptoms and H pylori infection. Long-segment Barrett's esophageal and IM of gastric antrum were designed as control. RESULTS: The prevalence of type III IM was significantly higher in SSBE than in CIM (63.33% vs 23.08%, P< 0.005). The CK7/20 immunoreactivity in SSBE showed mainly Barrett's pattern (76.66%), and the GERD symptoms in most cases which showed Barrett's pattern were positive, whereas H pylori infection was negative. However, the CK7/20 immunoreactivity in CIM was gastric pattern preponderantly (61.54%), but there were 23.08% cases that showed Barrett's pattern. H pylori infection in all cases which showed gastric pattern was significantly higher than those which showed Barrett's pattern (63.83% vs 19.30%, P< 0.005), whereas the GERD symptoms in gastric pattern were significantly lower than that in Barrett's pattern (21.28% vs 85.96%, P< 0.005). CONCLUSION: Distinction of SSBE from CIM should not be based on a single method; however, the combination of clinical characteristics, histology, mucin histochemistry, CK7/20 immunoreactivity, and endoscopic biopsy should be applied. Type III IM, presence of GERD symptoms, and Barrett's CK7/20 immunoreactivity pattern may support the diagnosis of SSBE, whereas non-type III IM, positive H pylori infection, and gastric CK7/20 immunoreactivity pattern may imply CIM.

Barrett Esophagus↗
PubMed1986

Special control of infection and rejection episodes after four years of cardiac transplantation at the University of Munich.

During the past 4 years, 36 orthotopic heart transplantations and two heart-lung transplantations were performed at Munich University Hospital. Immunosuppressive regimen consisted of cyclosporine A and low dose prednisone. The rejection diagnosis was based on daily cyto-immunological monitoring (CIM) and high frequency electrocardiography. In addition, viral, bacterial, and fungal infections were examined by CIM. The CIM is based on an evaluation of activated lymphocytes, lymphoblasts, and lymphocyte subsets in the mononuclear concentrate isolated from the peripheral blood by Ficoll Hypaque separation. Of the 38 patients, 24 are currently alive from 1 month to 4 years later (including one heart-lung recipient 1.5 years postoperatively). Altogether, 40 rejection episodes occurred among the patients. The diagnosis was based on CIM (sensitivity = 95%) and on endomyocardial biopsies (sensitivity = 95%). Control of rejection therapy was also done by using these methods. When the biopsies showed ongoing acute rejection, additional antithymocyte globulin or antilymphocyte globulin therapy was administered, relative to the CIM results. When using the endomyocardial biopsies for rejection control only, results showed a very low rate of two to three biopsies per patient in the first 3 months postoperatively. In addition, 16 infection periods were detected: five viral, six bacterial, four fungal, and one case of toxoplasmosis. The CIM showed typical hints of these inflammations in 12 cases (sensitivity = 75%) before clinical signs were visible. This immediately led to further diagnostic examinations and specific anti-infectious therapies, which were initiated early.

Journal Article↗
PubMedDate not supplied

Effects of perioperative cimetidine administration on peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: results of a randomized controlled clinical trial.

BACKGROUND/AIMS: Cimetidine (CIM) seems to have positive effects on the immune systems of cancer patients. This study was conducted to investigate the effects of perioperative administration of CIM on the peripheral blood lymphocytes, natural killer (NK) cells and tumor infiltrating lymphocytes (TIL) in patients with gastrointestinal (GI) cancer. METHODOLOGY: Forty-nine GI cancer patients were randomized into a treatment group which took CIM in the perioperative period, and a control group which did not take the drug. The treatment was initiated 7 days (d) before operation and continued until 10 d after surgery. At baseline examination, before operation, on the 2nd and the 10th postoperative d, peripheral blood T lymphocytes, helper T cells, T suppressor cells, and NK cells were measured by immunocytochemical method. The surgical specimens were examined for TIL response, and immunohistochemical study was performed to measure the proportion of T and B lymphocytes in the TIL population. RESULTS: In comparison with normal controls, both the treatment and the control groups had decreased T cells, helper T cells and NK cells at baseline. In the control group, total T cells, helper T cells and NK cells declined progressively with the disease course and the decreases became more profound after operation. From the baseline to the 2nd postoperative d, the proportion of total T cells, helper T cells, and NK cells went down from 60.5+/-4.6 to 56.2+/-3.8 percent, from 33.4+/-3.7 to 28.1+/-3.4 percent, and from 15.0+/-2.8 to 14.2+/-2.2 percent, respectively. On the other hand, there were significant improvements in these parameters after CIM treatment. On the 10th postoperative d, the treatment group had significantly higher percentages of total T cells, helper T cells and NK cells than control group. Moreover, CIM treatment also boosted the TIL response, as was reflected by findings that 68% (17/25) of the patients in the treatment group had significant TIL responses and only 25% (6/24) of the cases had discernible TIL response. CONCLUSIONS: Perioperative application of CIM to GI cancer patients could help restore the diminished cellular immunity boost TIL responses to tumor.

Adjuvants, Immunologic↗
PubMed1986

Mannitol potentiates cyclosporine nephrotoxicity.

A possible drug interaction between cyclosporine (CyA) and mannitol was tested for in female Wistar rats infused continuously with CyA 10 mg (40-50 mg/kg BW) in 24 ml mannitol 20% daily for 3 to 4 days (group CIM). For comparison, two other groups of rats were infused either with the same amount of CyA in 24 ml NaCl 0.9% (group CINa) or with the same amount of mannitol without CyA (group M). No animal of groups CINa or M, but 6 out of 10 group CIM rats developed severe oligo-anuric acute renal failure (ARF). Histologically massive vacuolisation of proximal tubular epithelia was found in the kidneys of CIM rats with ARF, while CIM rats without ARF showed minor to moderate degrees of vacuolisation. No vacuolisation was seen in groups CINa and M. Moderate amounts of tubular inclusion bodies and microcalcifications were detected in the kidneys of CIM rats without ARF and in those of CINa rats. To elucidate the mechanism of ARF, renal blood flow, creatinine clearance and proximal tubular pressures were measured in the kidneys of another series of CIM rats infused for 48-96 hours with CyA and mannitol. Renal blood flow and proximal tubular pressures in the kidneys of animals that had not or not yet developed ARF did not differ from those in rats infused with mannitol alone despite histological alterations with minor to moderate degrees of vacuolisation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Cimaterol-induced growth in rats: growth pattern and biochemical characteristics.

Sixty Sprague-Dawley female rats weighing 170 g were used to investigate the effect of cimaterol on the growth pattern and biochemical characteristics of skeletal muscles. Cimaterol (CIM) was mixed in a powdered rat chow at 10 ppm. A significant (P less than .01) improvement in the weight gain of CIM group was observed during the first 8 days of the 49-day trial period, followed by no significant improvement thereafter. When CIM was withdrawn from the diet, treated rats lost weight, eventually regressing to the same weight as control rats after 28 days. CIM-fed rats showed 28.6% (P less than .01) and 12.9% (P less than .05) increases in plantaris muscle weight over the control at 8 and 14 d, respectively. DNA concentration significantly (P less than .05) decreased, whereas RNA concentration increased at 3 d (31%) and 8 d (12.7%), but decreased at 14 d compared to the control. The increase in RNA concentration preceded the significant improvement of muscle weight in the CIM group. In the soleus muscle, there was no significant difference in muscle weight or DNA concentration between the control and CIM groups. Cimaterol-feeding significantly (P less than .05) increased the size of both type I and II fibers. The size increase of type II fibers in plantaris was twice that of type I fibers in soleus (34.2% vs 17.5%). This may explain why the plantaris muscle (type II predominant) showed a greater weight increase than the soleus muscle (type I predominant).

Animals↗
PubMed1984

Cimetidine interaction with dipotassium clorazepate disposition in the anesthetized dog.

Cimetidine (CIM) was used as an interacting agent on the disposition in dogs of dipotassium clorazepate ( CZP ) and its main metabolite nordiazepam (ND) in order to study some of the factors contributing to pharmacokinetic interspecies variation of benzodiazepines in dogs and man. A 0.5 mg/kg of body weight intravenous (i.v.) bolus dose of CZP was administered to 12 anesthetized mongrel dogs, 6 of them receiving also, 30 min before, a 1 mg/kg i.v. bolus dose of CIM followed by a constant i.v. infusion (1 mg/kg/hr) of CIM. Plasma ND and CZP concentrations were measured as a function of time with an high-performance liquid chromatography method. Plasma levels of CZP declined mono- and biexponentially in 1 and 5 dogs, respectively, for each group of animals. No statistically significant difference was found between CZP pharmacokinetic parameters when the 2 groups of dogs were compared. However, a 37% decrease in ND beta half-life, t1/2 beta, when CZP was associated with CIM, was found to be statistically significant. The i.v. administration of pure ND in two dogs, has shown that ND declines biexponentially with a t1/2 beta similar to the one estimated after CZP dosing in control animals. The hepatic metabolism of ND was found to be flow-independent and restrictive. The data, along with previously reported CIM interactions, suggest that several factors, which would be species-dependent, must be responsible of CIM effect on other drugs.

Anesthesia↗
PubMed1984

Compositional and molecular species analysis of phospholipids by high performance liquid chromatography coupled with chemical ionization mass spectrometry.

High performance liquid chromatography (HPLC) was combined with chemical ionization mass spectrometry (CIMS) by the use of a moving-belt interface. The technique was employed for the analysis of naturally occurring phospholipids. Positive and negative ion mass spectra of various phospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, and sphingomyelin were obtained in the chemical ionization mode with ammonia or methane as the reagent gas. Specific ions for individual phospholipid "bases" were identified. These ions were used in specific ion monitoring of the phospholipids during HPLC-CIMS. CIMS of each phospholipid also provided extensive information on the molecular species of the individual class of phospholipids. Relative abundance of different molecular species of each phospholipid as determined by CIMS agreed well with the results obtained by gas-liquid chromatography. Rat brain phospholipids were analyzed by HPLC-CIMS in about 15 minutes. Routinely, about 5 micrograms of individual phospholipid was analyzed by HPLC-CIMS, however, with specific ion monitoring the method provides a detection capability at the subnanogram level.

Animals↗