Development of analytical methods for hydrochloride salts of cardiocyclide,a new Russian class III antiarrhythmic

Cardiocyclide, a new Russian class III antiarrhythmic agent, was developed at the State V. V. Zakusov Science Research Institute Pharmacology, Russian Academy of Medical Sciences. The aims of the present work were to study the physicochemical properties of the hydrochloride salt of this agent (N¹-(3-diethylaminopropyl)-N¹-(p-nitrobenzoyl)aminoacetic acid N,N-dicyclohexylamide HCl) and to develop an analytical method for this compound. IR, ¹H NMR, and UV spectra were obtained for cardiocyclide; its solubility was studied; its melting temperature, weight loss on drying and the transparency, color, and pH of its solutions were determined. The purity of material containing compound I was determined by thin-layer chromatography; quantitative cardiocyclide contents were estimated by non-aqueous titration. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 8, pp. 42–45, August, 2007.     

Overview: Beyond guidelines and guidance—psychosocial perspectives on treatment interventions for young people with substance problems in the United Kingdom

Over the last two decades there has been accumulating evidence that both psychosocial and pharmacological treatment interventions can effect change in substance-misusing adults. Thus, treatment interventions implemented for young people with substance problems largely draw on the adult addiction experience and that of child and adolescent psychiatry and psychology. As young people with problematic drug use have different treatment needs, and require different interventions and services to those of adults, results of adult studies cannot necessarily be directly extrapolated to young people.

Over the last five years evidence has been rapidly mounting that treatment may potentially work in young people, but as yet it is not as extensive as that for adults. The interventions that appear most fruitful are those based on learning theory, e.g. cognitive behavioural therapy and family therapy. Outcome studies in young people demonstrate substantial variability in substance use and misuse following treatment. From the UK perspective, the evidence is almost entirely USA based, and these evaluations of non-UK treatment programmes for young people cannot be simply transferred or transported to UK healthcare settings. This has significant implications for practice and policy.

At this stage, 'guidelines' or 'guidance' that is available is either not directed at young people and/or is largely gleaned from the USA literature. In addition, it does not adequately capture the complexity of cases at front-line specialist settings. The management of young substance misusers in the UK is, in the main, 'beyond guidelines and guidance'.

The restricted treatment service network for young people in the UK makes the potential for undertaking studies on treatment effectiveness extremely limited, but because there is evidence of a growing number of young people requiring treatment, such specialist drug services require evaluation. Serious consideration of the establishment and funding of evaluation of treatment interventions to be delivered to young substance misusers in the UK is urgently needed.     

Adding Bupivacaine to High-potassium Cardioplegia Improves Function and Reduces Cellular Damage of Rat Isolated Hearts after Prolonged, Cold Storage

Background: Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone.

Methods: After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 [mu]m bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4[degrees]C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured.

Results: All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline.     

Oncolytic herpes viral therapy is effective in the treatment of hepatocellular carcinoma cell lines

The rising incidence of hepatocellular carcinoma (HCC) in western countries, along with the poor prognosis offered by present-day treatment modalities, makes novel therapies for this disease necessary. Oncolytic herpes simplex viruses (HSV) are replication-competent viruses that are highly effective in the treatment of a wide variety of experimental models of human malignancies. This study seeks to investigate the effectiveness of oncolytic herpes viruses in the treatment of primary HCC cell lines. Sixteen commercially available human HCC cell lines were studied. G207 is an attenuated, replication-competent, oncolytic HSV engineered to selectively replicate within cancer cells. Cell lines were tested for viral sensitivity to G207 and their ability to support viral replication using standard cytotoxicity and viral replication assays. Eleven of 16 cell lines were moderately to highly sensitive to G207 viral oncolysis. HCC cell lines additionally demonstrated the ability to support viral replication in vitro with as high as 800-fold amplification of the administered viral dose observed. G207 is cytotoxic to, and efficiently replicates within, HCC cell lines in vitro. From these data, we suggest that oncolytic HSV therapy may have a role in the treatment of HCC, and in vivo studies are warranted. Presented in part at the 2005 American Hepato-Pancreato-Biliary Association Congress, Hollywood, Florida, April 14–17, 2005. Supported by grants R01CA75461 and R01CA72632 from the National Institutes of Health, and by grant MBC-99366 from the American Cancer Society (Yuman Fong).     

Distraction Osteogenesis of Ankylosed Front Teeth with Subsequent Orthodontic Fine Adjustment

OBJECTIVE: Conventional therapeutic approaches to correct ankylosed anterior teeth in infraposition require compromises involving esthetics and function. The combined approach of distraction and early orthodontic fine adjustment, not yet established as a routine, promises better results concerning the bone conditions and gingival development. CASE HISTORIES: Both female patients had suffered a trauma to the front teeth during early mixed dentition resulting in ankylosed central incisors in infraposition. At the ages of 14 years and 2 months and 15 years and 2 months, respectively, we carried out segment distraction by means of a bone-supported internal distractor followed by orthodontic fine adjustment after having shortened the consolidation phase. Both ankylosed front teeth could be successfully aligned, leading to an increase in bone and harmonization of the gingival margin in the dental arch. At ten and 14 months after the conclusion of treatment, we observed only few deviations in the dental situation compared to posttherapeutic findings. CONCLUSION: From a functional and esthetic point of view, therapy involving combined orthodontics and surgery is superior to conventional therapy. Orthodontic fine adjustment should be considered as a continuation of the distraction procedure.     

Comparative assesment of gingival thickness using transgingival probing and ultrasonographic method.

A decided attitude of expectation among many patients has given a new perspective to regenerative and plastic periodonta surgery. With authors emphasizing on the importance of gingival thickness, attempts are being made to obtain necessary information atraumatically and rapidly. Hence in the present study an attempt has been made to compare the two methods of assessing gingival thickness i.e transgingival probing and ultrasonographic method and also assess the gingival thickness in relation to central incisor lateral incisor and canine in Indian population. The gingival thickness was assessed in patients with healthy gingiva by both the methods. It was observed that transgingival probing method significantly over estimated the thickness of gingiva than the ultrasonographic method and the thickness of gingiva varies with morphology of the crown. It was concluded that compared to transgingival probing ultrasonographic method assesses gingiva thickness more accurately, rapidly and atraumatically.