Reduction of paracetamol metabolism after hepatic resection

INTRODUCTION: Paracetamol is often used as an analgesic following hepatic resection. During liver resection, vascular clamping is carried out to reduce blood loss. Previous studies have described transient postoperative rises in serum aminotransferase levels and decreases in prothrombin time and factor V levels. We have examined paracetamol metabolism after liver resection. METHODS: A prospective observational study was performed. All patients undergoing liver resection were included. Propacetamol was given every 6 h. Blood samples for plasma paracetamol concentrations were collected before, 1 h after the end of the first injection (T1), just before the second injection (6 h: T6), and just before the fifth injection (24 h: T24). RESULTS: 37 patients were recruited. 13 had hepatic vascular exclusion (HVE group), 13 had portal triad clamping (PTC group) and 11 had abdominal surgery with no liver resection (NLR group: control group). At T6, the plasma paracetamol concentration in the HVE group was significantly higher than in the NLR groups; at T24, this concentration was significantly higher in the HVE group than in the NLR and PTC groups, and was higher in the PTC group than in the NLR group. Prothrombin time and factor V was significantly lower in the HVE group than in the PTC group on the first postoperative day. DISCUSSION: This study showed a reduction of paracetamol metabolism in the liver resection group with significantly increased paracetamol levels. However, the maximum mean plasma concentration reached was not clinically or toxicologically significant. For these reasons, we cannot suggest that paracetamol should or should not be avoided in patients undergoing liver resection.     

Implication of steady state concentrations of nitrite and nitrate metabolites of nitric oxide in plasma and whole blood in healthy human subjects

1. The aim of the present study was to determine whether the steady state NOx concentration reflects NOx formation in vivo. 2. A NO3- load study was performed after achieving NOx steady state. Chronological changes in NOx concentrations in plasma and whole blood samples from nine healthy subjects were determined by the HPLC-Griess system and NOx concentrations in erythrocytes were estimated as a possible NOx compartment influential in regulating plasma NOx concentrations. 3. Analysis was performed using the first-order one-compartment open model and the NOx formation rate was subsequently calculated. 4. The mean (+/-SEM) steady state NOx concentration of plasma (15.5 +/- 1.6 micromol/L), whole blood (12.8 +/- 1.2 micromol/L) and erythrocytes (11.9 +/- 0.7 micromol/L) did not correlate with the NOx formation rate in the compartments (0.50 +/- 0.05, 0.61 +/- 0.04 and 0.91 +/- 0.17 micromol/kg per h, respectively), whereas a significant correlation was found between the steady state NOx concentration and NOx elimination rate (Kel) in plasma (r=-0.69; P=0.04) and whole blood (r=-0.79; P=0.01). 5. Although there was no direct correlation between steady state NOx concentrations and serum creatinine levels, the correlation between half-life and serum creatinine levels was significant (plasma: r=0.60, P=0.02; whole blood: r=0.49, P=0.04). 6. Plasma NOx concentrations correlated significantly with erythrocyte NOx concentrations (r=0.92, P <0.01; erythrocyte NOx=0.66 x plasma NOx). 7. The results of the present study indicate that NOx does not accumulate excessively into erythrocytes at steady state and during a NO3- load and that the steady state NOx concentration in whole blood and plasma preferentially implies NOx elimination (mainly depending on renal function) rather than NOx formation.     

The effect of dosing regimen on the pharmacokinetics of risedronate

AIMS: To examine the effect of timing of a risedronate dose relative to food intake on the rate and extent of risedronate absorption following single-dose, oral administration to healthy male and female volunteers. METHODS: A single-dose, randomized, parallel study design was conducted with volunteers assigned to four treatment groups (31 or 32 subjects per group, 127 subjects total). Each subject was orally administered 30 mg risedronate. Group 1 was fasted for 10 h prior to and 4 h after dosing (fasted group); Groups 2 and 3 were fasted for 10 h and were dosed 1 and 0.5 h, respectively, before a high-fat breakfast; and Group 4 was dosed 2 h after a standard dinner. Blood and urine samples were collected for 168 h after dosing. Pharmacokinetic parameters were estimated by simultaneous analysis of risedronate serum concentration and urinary excretion rate-time data. RESULTS: Extent of risedronate absorption (AUC and Ae ) was comparable (P=0.4) in subjects dosed 2 h after dinner and 0.5 h before breakfast; however, a significantly greater extent of absorption occurred when risedronate was given 1 or 4 h prior to a meal (1.4- to 2.3-fold greater). Administration 0.5, 1, or 4 h prior to a meal resulted in a significantly greater rate of absorption (Cmax 2.8-, 3.5-, and 4.1-fold greater, respectively) when compared with 2 h after dinner. CONCLUSIONS: The comparable extent of risedronate absorption when administered either 0.5-1 h before breakfast or 2 h after an evening meal support previous clinical studies where risedronate was found to have similar effectiveness using these dosing regimens. This flexibility in the timing of risedronate administration may provide patients an alternative means to achieve the desired efficacy while maintaining their normal daily routine.     

Relationship between ALDH2 genotypes and choice of alcoholic beverages]

There are obviously individual differences in the choice for many kinds of alcoholic beverages such as beer, wine, whisky, sake, cocktail and so on. It is generally believed that these differences are related to acquired preferences in taste and smell, in addition to life style. However, the basis of these acquired preferences is not yet understood. It has been shown that around half of Japanese show a marked sensitivity to alcoholic beverages because of aversive reactions due to a catalytic deficiency in ALDH2 isozyme. Therefore, differences in ALDH2 genotypes may possibly influence the choice of alcoholic beverages because the individuals possessing the ALDH2*2 gene may prefer the alcoholic beverages containing lower concentrations of alcohol. A large population survey (320 males, 132 females) was conducted using questionnaires to investigate the relationship between ALDH2 genotypes and the choice of alcoholic beverages. Individuals with the homozygote of ALDH2*1 generally showed more preference for alcoholic beverages containing a higher concentration of alcohol than those with the heterozygote or the homozygote of ALDH2*2. It was noted that the latter groups preferred whisky and water, and sweet cocktails. Also, the choices for beer, whisky, and sake were significantly different between both genders. Our data suggested that individuals with ALDH2*2 prefer beverages with lower concentrations of alcohol due to an aversive reaction after drinking, and that there are obvious gender differences in the consumption as well as the choice for many alcoholic beverages.     

Intra-uterine pressure and serum ibuprofen: Observations after oral administration of 400 mg ibuprofen to a patient with primary dysmenorrhoea

Summary Intra-uterine pressure was recorded in a dysmenorrhoeic patient for 10 h before and after administration of a single dose of ibuprofen 400 mg. Bloodsamples were obtained at regular intervals during the recording for determination of the serum concentration of ibuprofen by reverse HPLC. The maximum serum concentration (37.4 µg Ml^–1) was achieved after 1 h and the terminal half-life of ibuprofen was approximately 2 h. A marked reduction in intra-uterine pressure and the severity of pain was recorded 1.5 h following the administration of ibuprofen. Despite low or non-detectable serum concentrations of ibuprofen after 4 h, intra-uterine pressure never regained the level recorded before treatment.     

Effect of probenecid on the excretion of ampicillin in human bile

1. Ampicillin concentrations were determined in serum and bile after intravenous injection into patients with T-tube bile drainage of 1 gram ampicillin before and during probenecid medication. The concentrations were followed up to fifteen hours after injection.2. Probenecid increased the half-life of ampicillin in serum from 74 minutes to 137 minutes.3. Ampicillin concentrations in bile were higher following probenecid medication and a concentration over 5 mug/ml was obtained for 3 h longer than before probenecid.4. The ampicillin concentrations in bile were approximately the same as those in serum both before and during probenecid medication suggesting passive transport of ampicillin from blood to bile.5. A combined treatment of ampicillin and probenecid might be of clinical value in the therapy of cholangitis and typhoid carriers.     

Effects of grapefruit juice on the absorption of levothyroxine

AIMS: Our aim was to study the effect of grapefruit juice on the pharmacokinetics of levothyroxine. METHODS: In a randomized cross-over study with two phases, 10 healthy subjects ingested 200 ml grapefruit juice or water (control) three times daily for 2 days. On day 3, a single 600 microg dose of levothyroxine was administered with 200 ml grapefruit juice or water, which was also ingested 1 h before and 1 h after levothyroxine. Serum concentrations of total thyroxine (T4) and thyroid-stimulating hormone (TSH) were measured up to 24 h. RESULTS: Grapefruit juice decreased slightly (11%; P < 0.01) the maximal increase of T4 concentration after ingestion of levothyroxine from 66.4 nmol l(-1) to 59.4 nmol l(-1) (95% CI on the difference -11.3, -2.7). The incremental areas under the serum T4 concentration-time curve (dAUC) during the first 4 and 6 h were also decreased slightly: dAUC(0,4 h) by 13% (P < 0.05), from 195 nmol l(-1) h to 169 nmol l(-1) h (95% CI -51, -1) and dAUC(0,6 h) by 9% (P = 0.085), from 298 nmol l(-1) h to 271 nmol l(-1) h (95% CI -58, 4). The decrease in the serum concentration of TSH (1.25 mU l(-1)) measured 24 h after ingestion of levothyroxine, was not altered by grapefruit juice. CONCLUSIONS: Grapefruit juice may slightly delay the absorption of levothyroxine, but it seems to have only a minor effect on its bioavailability. Accordingly, the clinical relevance of the grapefruit juice-levothyroxine interaction is likely to be small.     

A single sip of a strong alcoholic beverage causes exposure to carcinogenic concentrations of acetaldehyde in the oral cavity

The aim of this study was to explore oral exposure to carcinogenic (group 1) acetaldehyde after single sips of strong alcoholic beverages containing no or high concentrations of acetaldehyde.Eight volunteers tasted 5 ml of ethanol diluted to 40 vol.% with no acetaldehyde and 40 vol.% calvados containing 2400 μM acetaldehyde. Salivary acetaldehyde and ethanol concentrations were measured by gas chromatography. The protocol was repeated after ingestion of ethanol (0.5 g/kg body weight).Salivary acetaldehyde concentration was significantly higher after sipping calvados than after sipping ethanol at 30 s both with (215 vs. 128 μmol/l, p < 0.05) and without (258 vs. 89 μmol/l, p < 0.05) alcohol ingestion. From 2 min onwards there were no significant differences in the decreasing salivary acetaldehyde concentration, which remained above the level of carcinogenicity still at 10 min. The systemic alcohol distribution from blood to saliva had no additional effect on salivary acetaldehyde after sipping of the alcoholic beverages.Carcinogenic concentrations of acetaldehyde are produced from ethanol in the oral cavity instantly after a small sip of strong alcoholic beverage, and the exposure continues for at least 10 min. Acetaldehyde present in the beverage has a short-term effect on total acetaldehyde exposure.     

Effect of S-methylisothiourea in acetaminophen-induced hepatotoxicity in rat

Nitric oxide synthesized from inducible nitric oxide synthase (iNOS) plays role in acetaminophen (APAP)-induced liver damage. The present study was undertaken to evaluate the effect of iNOS inhibitor S-methylisothiourea (SMT) in APAP-induced hepatotoxicity in rats (1?g/kg, i.p.). SMT was (10, 30, and 100?mg/kg; i.p.) given 30?min before and 3?h after APAP administration. At 6 and 24?h, blood was collected to measure alanine transaminase (ALT), aspartate transaminase (AST), and nitrate plus nitrite (NOx) levels in serum. At 48?h, animals were sacrificed, and blood and liver tissues were collected for biochemical estimation. SMT reduced significantly the serum ALT, AST, and NOx levels at 24 and 48?h and liver NOx levels at 48?h as compared with APAP-treated control. The amount of peroxynitrite measured by rhodamine assay was significantly reduced by SMT, as compared with APAP-treated control group. SMT treatment (30?mg/kg) has significantly reduced the lipid peroxidation and protein carbonyl levels, increased SOD and catalase, and reduced glutathione and total thiol levels significantly as compared with APAP-treated control. SMT 30?mg/kg dose has protected animals from APAP-induced hypotension and reduced iNOS gene expression. Hepatocytes were isolated from animals, and effect of SMT on apoptosis, MTP, and ROS generation was studied, and their increased value in APAP intoxicated group was found to be significantly decreased by SMT (30?mg/kg) at 24 and 48?h. In conclusion, nitric oxide produced from iNOS plays important role in toxicity at late hours (24 to 48?h), and SMT inhibits iNOS and reduces oxidative and nitrosative stress.     

Zolpidem excretion in breast milk

Five, lactating, healthy white women were treated with a single 20 mg tablet of zolpidem 3-4 days after the delivery of a full term baby. The drug was administered at 20.00 h, 30 min after dinner, and milk samples were collected before and 3, 13 and 16 h. Venous blood 5 ml was taken before and 1.5, 3, 13, 16 h after zolpidem administration. The apparent elimination half life, estimated from plasma zolpidem concentrations was 2.6 h. The amount of zolpidem excreted in the milk at 3 h ranged between 0.76 and 3.88 micrograms, which represented 0.004 to 0.019% of the administered dose; no detectable (below 0.5 ng/ml) zolpidem was found in the milk at subsequent sampling times. The ratio of the zolpidem concentrations in breast milk and plasma at 3 h was 0.13. The apparent breast milk clearance of zolpidem, calculated from the ratio of the total amount of zolpidem excreted in milk to its AUC in plasma was 1.48 ml/h. The results show that the excretion of zolpidem in human milk is very low (below 0.02%) and that most of it takes place during the first 3 h following drug intake.     

A clinical trial of astromicin, a new aminoglycoside antibiotic, in thoracotomized patients and astromicin concentrations in the lung tissue

There have been no report on concentrations in human lung tissue of aminoglycoside antibiotics which are frequently used in combination with cephem antibiotics in the treatment of severe respiratory infections. The authors examined lung tissue concentration of astromicin (ASTM) during clinical trials in thoracotomized patients using intravenous drip infusion just before operation. And the following conclusions have been obtained: 1. The average peak serum level obtained upon intravenous drip infusion of ASTM 200 mg for 1 hour just before operation was 11.2 micrograms/ml at 1 hour after starting the administration and half-life of ASTM in beta phase was 2.90 hours. 2. ASTM concentrations in the lung tissue upon 1 hour intravenous drip infusion just before operation at a dose level of 200 mg reached a maximum at 2 hours after the start of the administration averaging 7.7 micrograms/ml and were 27.7-68.8% of serum peak level. 3. Bronchiolar concentrations of ASTM 200 mg upon 1 hour intravenous drip infusion just before operation were 33.0-72.3% of peak serum level. These concentrations appear to be sufficient for the treatment of target infections. 4. The 1 hour intravenous drip infusion of ASTM 200 mg appeared to be clinically safety and useful as was the intramuscular injection of ASTM 200 mg.     

Extract of Juglandaceae regia inhibits growth, in-vitro adherence, acid production and aggregation of Streptococcus mutans

Aqueous and alcoholic extracts from Juglandaceae regia, used as chewing sticks to maintain oral hygiene, were tested for their ability to inhibit the growth and some physiological functions of Streptococcus mutans. Both the aqueous and the alcoholic extract strongly inhibited the growth, in-vitro adherence, acid production and glucan-induced aggregation of S. mutans. At a concentration of 8% w/v, the aqueous extract produced a 95% inhibition (P < 0.05) of adherence of S. mutans to glass and a 40% inhibition (P < 0.05) of adherence to tooth surface. The alcoholic extract at a concentration of 10% w/v produced a 95% inhibition (P < 0.05) of adherence of S. mutans to glass and a 56% inhibition (P < 0.05) of adherence to tooth surface. At concentrations of 2% w/v the aqueous and alcoholic extracts significantly inhibited (P < 0.05) glucan-induced aggregation of S. mutans and the in-vitro salivary glycolytic reaction for up to 5 h. Bactericidal effects on S. mutans were also evident. At a concentration of 10% w/v, the zone of inhibition observed with the aqueous extract was 12+/-0.01 mm and that observed with the alcoholic extract was 12.6+/-0.02 mm. As the in-vitro studies had shown that both the aqueous and the alcoholic extract of J. regia, at concentrations of 10% w/v, could inhibit the growth as well as the acid-producing ability of S. mutans, they were tested at the same concentration for their activity in-vivo. Three subjects were employed. Parameters monitored were salivary bacterial count and salivary glycolysis. Mouth-rinsing with the aqueous but not the alcoholic extract significantly reduced total streptococcal counts in the salivary samples obtained up to, and including, 3 h after rinsing, compared with the counts obtained pre-rinsing or after placebo rinsing. Mouth-rinsing with the aqueous extract produced a 65%, 27% and 78% reduction (P < 0.05) in the streptococcal count in the salivary samples obtained 10 min, 1 h and 3 h after rinsing, respectively. Both the aqueous and the alcoholic extract also inhibited the glycolytic reaction by the salivary bacteria for up to 90 min post-rinsing. This study provides evidence to justify the use of J. regia sticks as an aid to maintain oral hygiene.     

Absence of a differential induction of cytochrome P450 2E1 by different alcoholic beverages in rats: implications for the aetiology of human oesophageal cancer

Alcohol is an important risk factor for human oesophageal cancer. There is evidence from epidemiological studies that some specific alcoholic drinks, e.g. Calvados apple brandy, are associated with a greater risk than others. Alcohol induces cytochrome P450 2E1 (CYP2E1) and the hypothesis was tested that different alcoholic beverages, containing a variety of alcoholic compounds, could differentially induce expression of cytochrome P450 enzymes. Twelve groups of five rats each were treated for 3 days with different alcoholic beverages (ethanol alone, whisky, farm-produced or commercial Calvados brandy, beer, cider, wine) adjusted to 4, 10 or 20% of ethanol in drinking water. Immunoblotting using a monoclonal antibody specific for rat CYP2E1 revealed a single protein band in liver microsomes. Densitometric quantitation of microsomal proteins demonstrated a significant two-, three- and sixfold increase in band intensity after treatment with ethanol concentrations of 4, 10 and 20% respectively, compared to control rats drinking water alone. There was a dose-dependent increase in liver microsomal metabolism of CYP2E1 substrates (para-nitrophenol and dimethylnitrosamine) in ethanol-treated rats. However, there were no significant differences in the level of CYP2E1 protein or enzymatic activity between the different alcoholic beverages at the same ethanol concentration. There was a slight increase in hepatic CYP1A-related enzymatic activities in the alcohol-treated rats compared to the controls, but no difference between the treated groups either with dose of ethanol or type of beverage. These data show that induction of CYP2E1 with acute alcohol treatment is predominantly determined by the ethanol content of the beverage. Received: 10 February 1997 / Accepted: 26 May 1997     

Effect of cimetidine on serum uric acid concentration

The effect of cimetidine therapy on serum uric acid concentration was studied in four healthy men with normal renal function. Beginning four days before the 16-day study, subjects were permitted no beverages containing caffeine or alcohol and no medications and were placed on a weight-maintenance, isocaloric, purine-free 152-meq-sodium diet. On days 1-12 one cimetidine 300-mg tablet was taken four times daily; on days 13-16 no cimetidine was taken. On each study day, serum uric acid and creatinine and urine uric acid and creatinine concentrations were determined. Daily mean values for serum uric acid, total uric acid excreted, and uric acid clearance were not significantly different from baseline. No significant change occurred in creatinine excreted or creatinine clearance. Cimetidine administration to healthy men with normal renal function did not significantly affect serum uric acid concentration or renal clearance of urate.     

A randomized trial to determine the change in alanine aminotransferase during 10 days of paracetamol (acetaminophen) administration in subjects who consume moderate amounts of alcohol

BACKGROUND: Previous studies have suggested that therapeutic doses of paracetamol (acetaminophen) are safe in alcoholic patients when administered for up to 3 days. However, 14 days of therapeutic doses of paracetamol has been associated with an increase in serum transaminases. AIM: To determine the effect of 10 days of the maximal therapeutic dose of paracetamol on serum alanine aminotransferase (ALT) activity in subjects who consume 1 to 3 alcoholic beverages per day. METHODS: This was a randomized, double blind, placebo-controlled trial. Subjects took 4 g of paracetamol (or placebo) daily for 10 days. Serum aspartate aminotransferase (AST), ALT, bilirubin and INR were measured at baseline, day 4 and day 11. Symptoms potentially related to liver injury were also recorded. RESULTS: Paracetamol and placebo groups had no change from baseline values at day 4, but the paracetamol group had an increase in mean ALT at day 11 of 8.7 IU/L. No subject developed symptoms of liver injury or met predefined criteria for hepatotoxicity or liver failure. CONCLUSION: Therapeutic dosing of paracetamol administered for 10 days appears to elevate serum ALT in moderate drinkers, but does not produce clinically evident liver injury.     

Effects of erdosteine on smoking-induced lipid peroxidation in healthy smokers

AIM: Oxidative stress caused by smoking has been implicated in many pulmonary diseases. Smoking causes reductions in plasma nitrate plus nitrite (NOx) concentrations and increases in plasma malondialdehyde (MDA) concentrations, which indicate oxidative stress and lipid peroxidation, respectively. In this study, we investigated the acute effects of smoking a single cigarette on the plasma concentrations of NOx and thiobarbituric acid reactive substances (TBARS) including MDA, and whether administration of erdosteine, a mucolytic and antioxidant agent, affects these parameters. METHODS: Thirty healthy smokers were included in the study. Subjects smoked a single cigarette in 10 minutes on the study day. For analysis of NOx, TBARS and cotinine, blood was drawn from each subject before and 5 and 30 minutes after smoking. The subjects were then randomly divided into two groups, one receiving placebo and the other erdosteine suspension 175mg/5mL twice daily for 1 month. After this treatment period, the same study protocol was carried out. Two subjects in the placebo and five subjects in the study group were excluded because of noncompliance. RESULTS: Twenty-three (14 female, 9 male) subjects completed the study. Their mean age was 32 +/- 8 years and their smoking history was 14 +/- 9 pack-years. Baseline NOx, TBARS and cotinine concentrations were similar between the groups. NOx concentrations decreased significantly after smoke exposure. At the end of the treatment period there were no significant differences in NOx, TBARS or cotinine concentrations between the groups. The concentration of TBARS after smoking decreased significantly in the erdosteine-treated group (at 5 minutes: 2.8 +/- 0.5 micromol/L before treatment and 2.3 +/- 0.3 micromol/L after treatment, p < 0.05; at 30 minutes: 2.8 +/- 0.5 micromol/L before treatment and 1.8 +/- 0.7 micromol/L after treatment, p < 0.05). Smoking history was significantly correlated with cotinine concentrations. CONCLUSION: Acute smoke exposure decreased plasma NOx concentrations in healthy smokers, and this was not changed with erdosteine treatment. However, significant decreases were noted in TBARS concentrations after smoke exposure in the group that received erdosteine, suggesting that short-term erdosteine administration might help prevent smoking-induced lipid peroxidation.     

Iron and alcohol content of traditional beers in rural Zimbabwe

OBJECTIVES: To determine the concentrations of iron and alcohol in traditional beer, as well as how these may be related to the brewing process. DESIGN: Cross sectional study. SETTING/SUBJECTS: Rural communities living in four of Zimbabwe's nine provinces. MAIN OUTCOME MEASURES: Ionic iron concentration and alcohol concentration in 94 different types of alcoholic beverages prepared in rural areas, and 18 commercially produced beers. RESULTS: The commonest types of traditional beer were a seven day beverage called 'doro rematanda', a by-product of this seven day beer called 'muchaiwa,' and a one-day beverage called 'chikokiyana'. Methods of preparation were similar in the four provinces. Median (Q1, Q3) ionic iron concentrations were 52 (31 to 75) mg/L for the seven-day beer (n = 51), 24 (18 to 36) mg/L for muchaiwa (n = 30) and 21 (17 to 63) mg/L for chikokiyana (n = 13). In contrast, ionic iron concentrations in 12 samples of commercially prepared clear beers were 0.1 mg/L and in commercial opaque beer were 3.6 mg/L. Mean (SD) alcohol concentration in traditional beer was 4.1 g/100 ml (+/- 0.873) compared to 2.8 g/100 ml +/- 1.394) in the muchaiwa and 3.6 g/100 ml (+/- 1.445) in the one day brew, chikokiyana. Mean alcohol concentrations in the three commercial beers are reportedly 3.5 g/100 ml in the opaque beer (Scud), and 4.7 to 5.0 g/ml in clear beer (Zambezi and Castle lagers). CONCLUSIONS: Several preparation methods lead to traditional fermented beverages with very high iron concentrations. Measures to prevent dietary iron overload should include all of these beverages in their scope.     

The concentration of ceftizoxime in serum and lung tissues and prophylaxis of postoperative infections

There are few clinical reports about the concentration of ceftizoxime (CZX) in lung tissues. At present, clinically, we report the concentration of the drug in serum and lung tissues on 26 cases of chest disease and an effect of the drug on prophylaxis of postoperative pulmonary infections. Our results are the following; The peak concentration of CZX in serum is 54.7 micrograms/ml at 1 hour after starting drip infusion of CZX 1 g. The serum half-life of CZX (beta phase) is 2.07 hours. The concentration of CZX in lung tissues is from 43.6 to 78.7% of serum level. CZX is useful to prophylaxis of postoperative infections after thoracotomy, especially in case of administration of CZX 1 g just before operation. Eruption was found in 1 of 26 cases. However, no side effects of the drug are noticed in other 25 cases.     

The use of caffeinated alcoholic beverages among underage drinkers: Results of a national survey

Objective

The mixing of alcoholic beverages with caffeine has been identified as a public health problem among college students; however, little is known about the consumption of such drinks among younger adolescents. We estimated the prevalence of caffeinated alcoholic beverage (CAB) use among a wide age range of underage drinkers, examined differences in traditional (i.e. self-mixed alcoholic beverages with soda, coffee and tea) and non-traditional CAB use (pre-mixed caffeinated alcoholic beverages or self-mixed alcoholic beverages with energy drinks or energy shots) among underage drinkers by age and other demographic characteristics, and examined differences in hazardous drinking behavior between CAB and non-CAB users.

Methods

We used an existing Internet panel maintained by Knowledge Networks, Inc. to assess the use of pre-mixed and self-mixed CABs in the past 30 days among a national sample of 1031 youth drinkers age 13–20. We conducted logistic regression analyses to estimate the relationship between traditional and non-traditional CAB use and risky drinking behavior as well as adverse outcomes of drinking, while controlling for age, gender, race/ethnicity, income, and general risk-taking (seat belt use).

Results

The overall prevalence of CAB use in the sample of underage drinkers was 52.4% (95% confidence interval [CI], 47.4%–57.4%). CAB prevalence was 48.4% among 13–15 year-old drinkers, 45.3% among 16–18 year-old drinkers, and 58.4% among 19–20 year-old drinkers. After controlling for other variables, we found a continuum of risk with non-traditional CAB use most significantly associated with binge drinking (odds ratio [OR] = 6.3), fighting (OR = 4.4), and alcohol-related injuries (OR = 5.6).

Conclusions

The problem of caffeinated alcoholic beverage use is not restricted to college-aged youth. The prevalence of CAB use among underage drinkers is higher than previously thought and begins in early adolescence. Adolescents who consume CABs, and particularly non-traditional CABs, are at increased risk of adverse outcomes.     

Decrease in plasma NOx concentration by isosorbide dinitrate,an organic nitrate ester

It has been suggested that isosorbide dinitrate (ISDN)-induced venodilation could be ascribed to preferential accumulation of the agent in venous tissues, resulting in higher concentrations of nitric oxide (NO). Here, the authors investigated whether the venodilating effect of ISDN is associated with a preferential increase in plasma concentrations of NOx (NO2- and NO3-, stable end-products of NO) in venous blood than arterial blood. Plasma NOx was measured by high-performance liquid chromatography-Griess system with a sensitivity of 0.01 microM for NO2- and 0.1 microM for NO3-. Arterial and venous blood samples were obtained after coronary angiography from the aorta and right atrium of patients with or without ischemic heart disease. Nicardipine, a calcium channel blocker, was used as a non-NO-related arteriovasodilator. At 1 mg i.v., it did not cause any changes in NOx concentration in arterial and venous blood irrespective of hemodynamic changes. However, ISDN (3 mg i.v.) increased NO2- and decreased NO3- in both arterial and venous blood, with concomitant venodilation. Further analysis revealed that plasma NO increased in the pulmonary circulation and this increase was preserved after nicardipine and ISDN, and that ISDN, but not nicardipine, increased plasma NO3- in the pulmonary circulation. The authors did not detect higher concentrations of NOx in venous blood relative to their level in arterial blood. Further studies are necessary to clarify the kinetics of NO and NO-related compounds in the whole body.