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At least 1,189 records · Page 66Linked to original sources
PubMed1983

Derivatives of 4,5,6,7-tetrahydro-7,8,8-trimethyl-3-phenylamino-4,7-methano-2H-indazole with hypoglycemic and hypotensive activities.

By reaction of camphor enamine (I) with phenyl isothiocyanate, the N-phenyl thiocarboxamide (II) was obtained in excellent yield, and in turn gave 4,5,6,7-tetrahydro-7,8,8-trimethyl-3-phenylamino-4,7-methano-2H-indazole (III) in very good yield by reaction with hydrazine hydrate. A series of N-substituted ureas (IV) were synthesized in satisfactory yield by reaction of (III) with alkyl and aryl isocyanates. Ureas (IV) showed in general hypoglycemic and in some cases hypotensive activity in rats, whereas only hypotensive activity was present in the thiocarboxamide (II). Effects on heart rate, antiinflammatory and antipyretic activities in rats, infiltration anesthesia and antiarrhythmic activity in mice, as well as antiacetylcholine activity in vitro, are also reported.

Anesthesia, Intravenous↗
PubMed1984

[Therapy of hyperhidrosis].

In the treatment of hyperhidrosis stabilization of psychovegetative functions is certainly desirable. However, autogenic exercise, hypnosis, psychotherapy as well as the administration of sedatives and tranquilizers serve only as adjuvant therapeutic measures. Systemic antihidrotics, like sage or camphor, proved ineffective; anticholinergics pose the risk of side effects. For topical therapy aldehydes, organic acids, and especially metallic salts are favorable. Tanning agents are of limited effect. Topical anticholinergics suppress sweating but provoke systemic side effects, if resorbed in larger quantities. Surgical treatment includes sympathetic blockade, sympathectomy, excision or curettage of eccrine glands, and cryotherapy or application of sclerosing agents. Concerning efficacy and risks of therapy only excision of axillary skin fields can be advocated. Among physical measures X-ray therapy is rendered obsolete. However, tap water iontophoresis is gaining increasing significance as an effective and safe treatment in palmar and plantar hyperhidrosis. In hyperhidrosis axillaris, palmaris, or plantaris topical application of aluminum chloride solution is emphasized as an efficacious treatment modality. If it fails, axillary skin fields can be excised and hyperhidrosis of palms or soles can be treated with tap water iontophoresis.

Aluminum Hydroxide↗
PubMed1981

Apparent differential response of nuclear envelope cytochrome P-450 following phenobarbital induction arising from a preferential loss during gradient purification.

We have investigated the response of rat liver nuclear, nuclear envelope, and microsomal cytochrome P-450 (or P-448) to various treatments. Responses of these subcellular fractions to 3-methylcholanthrene pretreatment were generally similar. In endoplasmic reticulum preparations, we observed an increase in cytochrome P-450 content following phenobarbital pretreatment, which was reduced by subsequent thioacetamide treatment. Nuclear envelope cytochrome P-450 was apparently not modulated by these treatments, although nuclear cytochrome P-450 content was increased by phenobarbital. When endoplasmic reticulum preparations were subjected to treatments paralleling those used in nuclear envelope purification, we found a preferential loss of cytochrome P-450 from phenobarbital-pretreated preparations, with a loss of camphor-binding ability. The data point to potential problems with use of isolated nuclear envelopes as a representative model for nuclear metabolism of carcinogens, including low total recoveries and enrichments, and the potential for selective or differential recovery of cytochrome P-450 populations following various modes of induction or reduction.

Animals↗
PubMed1983

Structural studies of cytochrome P-450 using small angle x-ray scattering.

We have employed small angle x-ray scattering to examine the solution conformation of cytochrome P-450cam in the presence and absence of its substrate, camphor. The radius of gyration (Rg) of the protein is found to be 23.9 +/- 0.2 A in both states. Comparison of the radius of gyration with that expected for a spherical protein of the same molecular weight indicates that P-450 is an elongated molecule and that its shape may best be approximated by a cylinder about 30 A in diameter and 80 A in length.

Cytochrome P-450 Enzyme System↗
PubMed1982

Structural features of isozyme 2 of liver microsomal cytochrome P-450. Identification of a highly conserved cysteine-containing peptide.

Earlier findings in several laboratories have suggested that the various forms of cytochrome P-450 within a given species or from different species are not closely related. However, our present studies on the primary structure of the phenobarbital-inducible cytochrome from rabbit liver microsomes (P-450LM2) show that this protein is about 80% identical to the corresponding rat protein (P-450b), the sequence of which was recently deduced by others. For example, of the first 70 residues of the NH2-terminal sequences, 52 are identical, with most differences structurally conservative and attributable to point mutations. No evidence was found for heterogeneity in the region of the rabbit cytochrome corresponding to the variable region proposed for the rat cytochrome. A comparison of the known primary structure of P-450LM2 with that of P-450b and that of the bacterial camphor-hydroxylating cytochrome (P-450cam) as recently reported by others reveals only one highly conserved cysteine-containing peptide present in approximately the same position in each cytochrome. This peptide in the rabbit enzyme, -Arg-Ile-Gln-Glu-Glu-Ala-Arg-Cys147-Leu-Val-Glu-Glu-Leu-Arg-, and the corresponding peptides containing Cys152 in P-450b and Cys134 in P-450cam may serve an essential function such as providing the axial thiolate ligand to the heme iron atom.

Amino Acid Sequence↗
PubMedDate not supplied

[Electrophysiological study of sex pheromone reception in the boar, Sus scrofa].

Electroolfactograms were recorded in isolated olfactory epithelium of pigs, both females and castrated males, of various age. The boar pheromone, 5 alpha-androst-16-en-3-one, elicited negative electrical responses up to 2 mV in many preparations. The threshold response corresponded to as low as 10(-9) g of the pheromone on a filter paper. The specific anosmia to the boar pheromone was discovered in few preparations, where responses to the pheromone were absent and the sensitivity to common odour substances (butyl acetate, camphor, butyric acid, etc.) was unchanged.

Animals↗
PubMed1976

Drug therapy in colonial and revolutionary America.

Drug therapy during the Colonial and Revolutionary War period in America is discussed. Therapy in the 17th and 18th centuries remained largely symptomatic rather than curative. Treatment included such "depletion" measures as purging, sweating, bleeding, blistering and vomiting. Purgatives, emetics, opium, cinchona bark, camphor, potassium nitrate and mercury were among the most widely used drugs. European herbals, dispensatories and textbooks were used in the American colonies, and beginning in the early 18th century, British "patent medicines" were imported. During the Revolutionary War, the supply of drugs from Britain was cut off. The Continental Congress established laboratories and storehouses to serve the needs of the army.

Cinchona↗
PubMed1994

[Croupous pneumonia: current problems and means for their resolution].

Croupous pneumonia makes up to 7-8% of all pneumonia cases in different regions of the country. 83 lethal outcomes have been studied. In 46 cases pneumonia was primary illness and the direct cause of death. In case a pneumonia is diagnosed an urgent hospitalization and penicillin treatment (maximum effect on pneumococcus is ensured with 1.8-2.4 million units per day) are necessary. For the prevention of acute cardiovascular insufficiency camphor is prescribed for 2-3 days. Mucolytic preparations and--after normalization of temperature--physiotherapeutic methods and therapeutic exercises are used for treatment. In 25-46.6% of lethal cases pneumonia is not diagnosed in their lifetime. Late hospitalization influencing illness's outcome takes place in 73% of cases.

Adolescent↗
PubMed1994

[Determination of tetramethylpyrazine and borneol in human plasma by GC-MSD].

A GC-MSD method for the determination of tetramethylpyrazine (TMP) and borneol in plasma is described. TMP and borneol were extracted with hexane-dichloromethane (10:1, V/V). Camphor was used as the internal standard. The average recoveries of TMP and borneol were 87.38% and 97.32% with relative standard deviation 1.90% to 6.21%, respectively. The method was successfully used to determine plasma borneol concentration following sublingual administration of 20 pills of Suxiao Jiuxin Wan to healthy volunteers (n = 10). The pharmacokinetic parameters have been listed in this paper.

Adult↗
PubMed1977

Gas-liquid chromatographic determination of solvents in commercial nail lacquer preparations.

A gas-liquid chromatographic (GLC) method has been developed for the determination of 5 solvents (butanol, butyl acetate, ethyl acetate, 2-propanol, and toluene) and camphor in commerical nail lacquer preparations. Resins and pigments are first precipitated from the solvents by dilution with isooctane. n-Propyl acetate is then added as an internal standard to the isooctane solution of solvents and the mixture is analyzed by temperature-programmed GLC. Analyses at 3 concentration levels (4, 20, and 40%) with 4 determinations at each level gave good recoveries.

Chromatography, Gas↗
PubMed1977

[Differentiated treatment and prevention of arrhythmias in myocardial infarct].

Monitoring and electrocardiographic observations were conducted in 900 patients during the acute and subacute periods of myocardial infarction. It was found that without preventive therapy arrhythmias develop in 85% of the patients, and with preventive antiarrhythmic treatment--in 75.5%. A combination of two and more types of arrhythmias was encountered in 42% of the cases. In the presence of routine therapy for myocardial infarction individual antiarrhythmic drugs displayed different efficacy. In supraventricular forms of arrhythmias the most effective drugs are Chinidin and Chinidin-Durules, Inderal and Hiluritmal, in ventricular forms--Lidokaine, Chinidin, Novocainamide, Inderal, Hiluritmal. A combined employment of these drugs against the background of potassium and magnesium salts administration, Inosie-F, water-soluble camphor and Cocarboxylase promoted the restoration of a normal sinus rhythm in 85% of the cases. When the drug therapy produced no antiarrhythmic effect and ventricular fibrillation developed, electroimpulse therapy was employed. In persistent atrioventricular blocks only cardiostimulation was effective.

Anti-Arrhythmia Agents↗
PubMed1977

Topical treatment of herpes labialis with chloroform.

The efficacy of topical chloroform treatment of herpes labialis (HL) was evaluated in 50 patients with culture-verified HL. Treatment was begun within 48 hours of lesion onset, with either chloroform or camphor-in-oil placebo applied locally once a day for three days. Patients were observed daily by one investigator who also cultured and photographed the lesions. The photographs were evaluated by two other investigators. By direct observation, the time for scab formation was significantly less in the group treated with chloroform (P less than .01). No difference in time to healing was noted. Blind evaluation of the serial photographs showed a trend for more rapid scab formation and healing in patients treated with chloroform, but the differences were not significant. The minimal benefit derived from topical chloroform therapy of HL does not appear sufficient to recommend its routine use.

Administration, Topical↗
PubMed1998

Absorption of the new anxiolytic compound deramciclane in rats, dogs and rabbits.

The absorption of deramciclane fumarate ((1R,2S,4R)-(-)-N,N-dimethyl-2-[(1,7,7-trimethyl-2-phenylbicyclo [2,2,1] hept-2-yl) oxy] ethane amine-2-(E)-butenedioate (1:1), CAS 120444-78-8, EGIS-3886), a new anxiolytic compound, was studied in rats, dogs and rabbits by using 3H-camphor- or 14C-phenyl-labelled radioisomers of the substance. The compound was readily absorbed from the intestinal tract after oral administration. The absorption of 14C-deramciclane was also studied from the isolated intestinal loops of rats (duodenal, jejunal, ileal loops) and dogs (duodenal loop). The absorption was faster in rats and rabbits than in dogs (tmax = 1 h or 6 h, respectively). The radioactivity was not absorbed from the isolated stomach of any species studied for 2 h. Meanwhile, the substance was not decomposed by the gastric juice, as it has been proved by TLC and MS analyses. Deramciclane is preferentially excreted via the bile. The intensity of its bile excretion is higher in rats than in dogs. Higher plasma levels of labelled deramciclane were found in female than in male rats.

Animals↗
PubMedDate not supplied

[Anniversaries of the Serbian Medical Society. 60 years since its founding. The dream is fulfilled--the home of the Serbian Medical Society is opened].

The Serbian Medical Society was founded in Belgrade in 1872, 126 years ago. At that time, Serbia was liberated from the Ottoman domination, and was one of some thirty existing independent states gaining international recognition in 1878. In 1932 an old dream has been fulfilled--on the occasion of the 60th anniversary of the existence and activity of the Serbian Medical Society--the home of Serbian Medical Society was opened. A 30-year-long period in which the building of the Home was one of the main preoccupations and a "guiding light" of Serbian doctors thus ended. Money from charitable funds was used, which caused certain benefactors to be praised as noted personalities. Medical practice in those days was in the state of choice. There were no means for adequate treatment of certain ailments, and therapy without realistic scientific base was given, often covered by fictitious reasons. This was especially true for tuberculosis and cancer. Under the pretext of the introduction of "new therapeutical approaches" into medical practice and treatment, diverse pharmaceutical formulas were introduced without knowledge of their real effect--injections of milk, drug containing animal embrional cells and special attention was paid to transplantation of the sexual glands. The injection of "camphor oil" (5 cc) was thus "recommended, harmless but useless". The treatment of tuberculosis, which domineered the pathology of population, was very chaotic. The greatest number of drugs for "successful cure" were to be found here. Most commotion was caused by the so-called Friedman's cure for tuberculosis which was rejected only after vigorous debates. Our drug "Joannin" on the basis of "the old tuberculine" was also represented in this confusion (and Koch himself was forced to recant it). This medicament was also hailed as "successful cure". The origin of serious scientific efforts, however, are to be found around newly formed journal "Medicinski pregled", which attracted new and progressive contributors. At this time, the newly formed Ministry of Public Health started a campaign for the introduction of a modern organization of the health care and the inclusion of all population in it. However, in a country devastated by war and stricken by poverity, annomalies in the functioning of the health care existed, as financial preconditions did not exist and healt insurance was still in its infancy. This made the status of doctors difficult, causing long debates in the Serbian Medical Society and fierce criticism of the Ministry of Public Health. The responsible persons were accused of introducing and promoting communist ideas and revolution under the duise of health care for the poipulation.

History, 19th Century↗
PubMed1996

Distributed automated docking of flexible ligands to proteins: parallel applications of AutoDock 2.4.

AutoDock 2.4 predicts the bound conformations of a small, flexible ligand to a nonflexible macromolecular target of known structure. The technique combines simulated annealing for conformation searching with a rapid grid-based method of energy evaluation based on the AMBER force field. AutoDock has been optimized in performance without sacrificing accuracy; it incorporates many enhancements and additions, including an intuitive interface. We have developed a set of tools for launching and analyzing many independent docking jobs in parallel on a heterogeneous network of UNIX-based workstations. This paper describes the current release, and the results of a suite of diverse test systems. We also present the results of a systematic investigation into the effects of varying simulated-annealing parameters on molecular docking. We show that even for ligands with a large number of degrees of freedom, root-mean-square deviations of less than 1 A from the crystallographic conformation are obtained for the lowest-energy dockings, although fewer dockings find the crystallographic conformation when there are more degrees of freedom.

Azepines↗
PubMed1998

The substrate specificity of cytochrome P450cam.

The catalytic turnover of xenobiotics by cytochrome P450cam results in both the formation of organic metabolites and the uncoupled production of H2O2, and H2O. Previous studies have shown that a receptor-constrained three-dimensional screening program (DOCK) can be used to identify potential ligands (ergo substrates) for the enzyme (De Voss, J. J.; Sibbesen, O.; Zhang, Z.; Ortiz de Montellano, P. R. J. Am. Chem. Soc. 1997, 119, 5489). A new set of 10 compounds has now been examined to further test the substrate specificity of P450cam and the ability of DOCK to identify substrates for this enzyme. The results expand the known specificity of P450cam and define limitations in the use of DOCK to predict its substrate specificity.

Camphor↗
PubMed2000

Conformational relaxation in hemoproteins: the cytochrome P-450cam case.

Photodissociation of (CO)P-450(cam)(substrate) complexes was found to trigger a conformational relaxation process that interferes with ligand rebinding at temperatures as low as 140 K even though the protein conformational substates (CS(1)) remain frozen. To analyze the rebinding and relaxation kinetics, we developed a model that takes the distribution of relaxation rates explicitly into account and in which rebinding and relaxation rates are connected by a linear free energy relation. In all complexes heme relaxation occurs first and is probably faster than 100 ns even at 77 K. This is the only process found in substrate-free P-450(cam). Above 140 K and in the presence of a substrate, this initial, fast rebinding state (P) progressively relaxes to another state (P degrees ) in which rebinding is slower. The relaxation rate is independent of solvent rigidity and is governed by the protein's internal dynamics. Rebinding enthalpies in P and P degrees as well as the enthalpy shift brought about by relaxation correlate with the substrate propensity to block access to the iron site. In P degrees the barrier is higher because the substrate is closer to the heme normal and exerts more steric repulsion for CO binding. The relaxation process implies the return of substrate and heme to their ligand-free positions in which access to the heme is reduced.

Adamantane↗