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Biomedical subjects

B Farkas

Publications and source records attributed to B Farkas.

At least 19 recordsLinked to original sources
PubMed2003

BGP-15, a hydroximic acid derivative, protects against cisplatin- or taxol-induced peripheral neuropathy in rats.

The neuroprotective effect of BGP-15 against peripheral sensory neuropathy was studied in rats that were exposed to short-term cisplatin or taxol administration. The changes of nerve conduction velocity were determined in situ after treating the Wistar rats with BGP-15 (50, 100, and 200 mg/kg po daily doses throughout the experiment), cisplatin (1.5 mg/kg ip daily dose for 5 days), or taxol (5.0 mg/kg ip daily dose every other day in a 10-day interval) alone or giving the test compound in combination with cisplatin or taxol. Electrophysiological recordings were carried out in vivo by stimulating the sciatic nerve at both sciatic notch and ankle site. Neither motor nor sensory nerve conduction velocity was altered by any dose level of BGP-15 tested. Both anticancer drugs decreased the sensory nerve conduction velocity (SNCV). BGP-15 treatment prevented the impairment of SNCV either in part or totally in the cisplatin- or taxol-treated groups. This neuroprotective potential of BGP-15 could be well correlated with its recently described poly(ADP-ribose) polymerase- inhibitory effect and its ability to protect against the damages induced by the increased level of reactive oxygen species in response to anticancer treatment.

Animals↗
PubMed2002

Terbinafine (Lamisil) treatment of toenail onychomycosis in patients with insulin-dependent and non-insulin-dependent diabetes mellitus: a multicentre trial.

BACKGROUND: Diabetes mellitus (DM) affects an estimated 175 million people world-wide. Approximately one-third of patients with DM have toenail onychomycosis. OBJECTIVES: To determine the efficacy and safety of terbinafine treatment of toenail onychomycosis in patients with DM receiving insulin and/or oral antidiabetic agents. Special interest was focused on potential drug interactions with oral hypoglycaemic substances. METHODS: In a multicentre trial, patients suffering from insulin-dependent DM (IDDM) or non- insulin-dependent DM (NIDDM) with toenail onychomycosis were treated for 12 weeks with oral terbinafine 250 mg daily and followed up to 48 weeks. In addition to clinical, mycological and laboratory investigations, blood glucose levels were monitored. RESULTS: At the end of the trial (week 48), a mycological cure rate of 73% was achieved. The rates of clinical cure and complete cure (mycological cure plus clinical cure) were 57% and 48%, respectively. There was no statistically significant difference between the NIDDM and IDDM groups with respect to the cure rates (P > 0.05). No hypoglycaemic episode was reported and none of the patients had hypoglycaemia during the treatment phase. CONCLUSIONS: With excellent cure rates and a good tolerability profile, terbinafine should continue to be a drug of choice for the treatment of toenail onychomycosis in the rising number of NIDDM patients receiving multiple medication.

Adolescent↗
PubMed2002

Effect of orexin-A on discharge rate of rat suprachiasmatic nucleus neurons in vitro.

The suprachiasmatic nuclei (SCN) constitute the principal pacemaker of the circadian timing system in mammals. The generated rhythm is forwarded mostly through projections to various hypothalamic nuclei. On the other hand, the regulated processes feedback to the SCN. One of the possible feedback pathways is the orexinergic projection from the lateral hypothalamus. Orexins are recently identified neuropeptides with an overall facilitatory effect on waking behaviors. Orexinergic fibers are widely distributed throughout the brain and are also present in the SCN. In this study we examined the effect of orexin-A on the spontaneous activity of rat SCN cell in vitro. Neurons showed 2 different firing pattern (continuous-regular, intermittent-irregular). Orexin-A increased firing rate in both cell types at 10(-8) M concentration, but caused a clear suppression of neuronal activity at 10(-7) M. Continuously firing neurons were less responsive than those firing intermittently. These results show that orexin-A may play a role in the modulation of the circadian pacemaker function. The neuropeptide might exert both direct, postsynaptic effects on SCN neurons and indirect, presynaptic effects on excitatory and inhibitory terminals. The dose-dependent modification of the firing rate indicate that the weight of these factors changes with the concentration of orexin-A.

Action Potentials↗
PubMed2000

BGP-15, a nicotinic amidoxime derivate protecting heart from ischemia reperfusion injury through modulation of poly(ADP-ribose) polymerase.

The protective effect of O-(3-piperidino-2-hydroxy-1-propyl)nicotinic amidoxime (BGP-15) against ischemia-reperfusion-induced injury was studied in the Langendorff heart perfusion system. To understand the molecular mechanism of the cardioprotection, the effect of BGP-15 on ischemic-reperfusion-induced reactive oxygen species (ROS) formation, lipid peroxidation single-strand DNA break formation, NAD(+) catabolism, and endogenous ADP-ribosylation reactions were investigated. These studies showed that BGP-15 significantly decreased leakage of lactate dehydrogenase, creatine kinase, and aspartate aminotransferase in reperfused hearts, and reduced the rate of NAD(+) catabolism. In addition, BGP-15 dramatically decreased the ischemia-reperfusion-induced self-ADP-ribosylation of nuclear poly(ADP-ribose) polymerase(PARP) and the mono-ADP-ribosylation of an endoplasmic reticulum chaperone GRP78. These data raise the possibility that BGP-15 may have a direct inhibitory effect on PARP. This hypothesis was tested on isolated enzyme, and kinetic analysis showed a mixed-type (noncompetitive) inhibition with a K(i) = 57 +/- 6 microM. Furthermore, BGP-15 decreased levels of ROS, lipid peroxidation, and single-strand DNA breaks in reperfused hearts. These data suggest that PARP may be an important molecular target of BGP-15 and that BGP-15 decreases ROS levels and cell injury during ischemia-reperfusion in the heart by inhibiting PARP activity.

ADP Ribose Transferases↗
PubMed2000

Development of spherical crystals of acetylsalicylic acid for direct tablet-making.

The production of spherical crystals has recently gained great attention due to the fact that the crystal habit (form, surface, size, etc.) can be modified during the crystallization process. Spherical crystals of ASA were developed by non-typical and typical spherical crystallization techniques. The non-typical spherical crystallization process (conventional stirred tank method) resulted in few monocrystals and non-spherical crystal agglomerates. The typical spherical crystallization process was carried out by the three solvent-system (ethanol-water-carbon tetrachloride). The products were qualified by morphological study, NIR investigation, salicylic acid content, dissolution rate, studies on flowability, compactibility, cohesivity and tablettability. The results demonstrate that only typical spherical crystallization can be recommended for the production of spherical crystals of ASA. Only product made by this technique shows excellent flow properties and favourable compactibility, cohesiveness and tablettability values.

Aspirin↗
PubMed1999

Impairment of neurogenic inflammatory and anti-inflammatory responses in diabetic rats.

The effect was studied of a primary (preconditioning) neurogenic inflammatory challenge induced by electrical stimulation of the peripheral stump of the sciatic nerve (20 V, 0.5 ms, 5 Hz, for 5 min) on neurogenic oedema (5 min later) induced by stimulation of the contralateral sciatic nerve. Plasma extravasation due to the second stimulation was decreased by 52.7+/-3.1% (P<0.01) in normal animals and by 29.7+/-2.2 and 18.1+/-1.5% with 50 mg/kg streptozotocin pretreatment i.v. 4 and 8 weeks previously, respectively. Subsequently, bilateral sciatic nerve stimulation increased baseline plasma somatostatin levels from 6.4+/-0.3, 11. 7+/-1.4, and 16.8+/-3.8 to 28.3+/-2.9 (P<0.01), 17.9+/-3.7, and 25. 1+/-1.7 pmol/l in normal, and 4- and 8-week diabetic animals, respectively. We conclude that experimental diabetes impairs the capability of a preconditioning neurogenic inflammatory episode to elicit a systemic anti-inflammatory effect. This is accompanied by a deficiency in elevation of the plasma somatostatin level in response to nerve stimulation, although the baseline plasma somatostatin level increases proportionally to the duration of experimental diabetes.

Animals↗
PubMed1999

Substance P radioimmunoassay for quantitative characterization of sensory neurotransmitter release.

In the present work we report the development of a new radioimmunoassay method for measuring the substance P content liberated from isolated rat tracheae in response to electrical or chemical (capsaicin, resiniferatoxin, piperine) stimulation. The amount of substance P released by electrical stimulation has been found to be dependent on the number of pulses and chemically elicited substance P release also proved to be dose-dependent. Our findings reinforce previous data that resiniferatoxin is approximately 100 times more potent than capsaicin and the potency ratio between piperine and capsaicin is 1/50.

Alkaloids↗
PubMed1998

[Spherical crystallization in pharmaceutical technology].

Physical properties of crystals, such as size, crystal size distribution and morphology, may predetermine the usefulness of crystalline materials in many pharmaceutical application. The above properties can be regulated with the crystallization process. The spherical crystals are suitable for direct tablet-making because of their better flowability and compressibility properties. These crystals can be used in the filling of the capsule. In this work, the spherical crystals such as "single crystal", "poly-crystals" and agglomerates with other excipients are collected from the literature and the experimental results of the authors. A close cooperation between chemists and the pharmaceutical technologists can help for doing steps in this field.

Chemistry, Physical↗
PubMed1997

Bimoclomol: a nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects.

Preservation of the chemical architecture of a cell or of an organism under changing and perhaps stressful conditions is termed homeostasis. An integral feature of homeostasis is the rapid expression of genes whose products are specifically dedicated to protect cellular functions against stress. One of the best known mechanisms protecting cells from various stresses is the heat-shock response which results in the induction of the synthesis of heat-shock proteins (HSPs or stress proteins). A large body of information supports that stress proteins--many of them molecular chaperones--are crucial for the maintenance of cell integrity during normal growth as well as during pathophysiological conditions, and thus can be considered "homeostatic proteins." Recently emphasis is being placed on the potential use of these proteins in preventing and/or treating diseases. Therefore, it would be of great therapeutic benefit to discover compounds that are clinically safe yet able to induce the accumulation of HSPs in patients with chronic disorders such as diabetes mellitus, heart disease or kidney failure. Here we show that a novel cytoprotective hydroxylamine derivative, [2-hydroxy-3-(1-piperidinyl) propoxy]-3-pyridinecarboximidoil-chloride maleate, Bimoclomol, facilitates the formation of chaperone molecules in eukaryotic cells by inducing or amplifying expression of heat-shock genes. The cytoprotective effects observed under several experimental conditions, including a murine model of ischemia and wound healing in the diabetic rat, are likely mediated by the coordinate expression of all major HSPs. This nontoxic drug, which is under Phase II clinical trials, has enormous potential therapeutic applications.

Animals↗
PubMed1994

The interleukin-8 receptor: a potential target for antipsoriatic therapy?

Interleukin-8 is assumed to play a central role in the pathogenesis of psoriasis. Since an increased expression of the interleukin-8 receptor has been observed both in polymorphonuclear leukocytes and in affected psoriatic epidermis, we were interested in whether the interleukin-8 receptor could be a molecular target of antipsoriatic compounds. Cyclosporine, calcitriol, calcipotriol or dithranol caused a dose-dependent decrease in interleukin-8 binding to cultured human keratinocytes, while interleukin-8 binding to granulocytes was not affected. In addition, the interleukin-8-induced human leukocyte antigen-DR (HLA-DR) expression of keratinocytes was nearly completely blocked by treatment of the cells with these substances. The inhibition of the keratinocyte interleukin-8 receptor and its function by antipsoriatic drugs may contribute to their therapeutic action.

Anthralin↗
PubMed1994

[Functional study of the regeneration of nerve fibers after keratinocyte transplantation].

The functional regeneration of sensory nerves was investigated in 5 patients with skin defects (caused by leg ulcers, a burn or fasciitis necrotisans) after transplantation with a keratinocyte suspension. In this area, first the pain sense and soon after wards the cold and heat sense returned, followed finally by the flare reaction caused by the mustard oil test. No sweat production could be observed during the study, because sweat glands were not found after the keratinocyte transplantation. The reinnervation course is roughly the same for skin defects covered with split skin graft or with a keratinocyte suspension.

Adult↗
PubMed1993

"Clip-stone" filiation within the biliary tract.

A case of cholangitis due to the migration of a metal clip used for surgical cholecystectomy 4 years earlier, is reported. The diagnostic approach and therapeutic options, either endoscopic or surgical are discussed. The use of resorbable clips during the performance of laparoscopic cholecystectomy should avoid this type of complication.

Aged↗
PubMed1991

Repeated treatment with dithranol induces a tolerance reaction in keratinocytes in vitro.

The hyperproliferative human keratinocyte line (HaCaT) was tested for dithranol tolerance (tachyphylaxis) at the cellular level. At day 4 after seeding, keratinocytes were treated with 0.3 or 1.0 microM dithranol. Data were compared with those from experiments including additional pretreatments with 0.3 microM at day 3, or at days 1 and 3. Protein content, DNA synthesis and protein synthesis (incorporation of 3H-thymidine and 14C-amino acids per protein) were determined at 24, 48 and 72 h after the last drug exposure. Protein content of attached cells decreased in relation to dose and frequency of treatments. Inhibition of DNA and protein synthesis (38.2% and 32.3%, respectively) also occurred 24 h after a single treatment with 0.3 microM dithranol, but was only 18.4% and 9.1% after pretreatment twice with 0.3 microM dithranol. This tolerance reaction in vitro, after repeated dithranol exposure of human keratinocytes, may be explained by a selective loss of drug-sensitive cells.

Anthralin↗
PubMed1990

Lactate dehydrogenase release as an indicator of dithranol-induced membrane injury in cultured human keratinocytes. A time profile study.

HaCaT cells, a rapidly multiplying human keratinocyte line, were tested for their sensitivity to antipsoriatic dithranol with regard to classical proliferation parameters and for the drug's action on the plasma membrane integrity by the dose- and time-dependent release of cytosolic lactate dehydrogenase (LDH). In the case of 3H thymidine as well as 14C amino acid incorporation the 50% inhibition concentration (IC50) was 0.2 microM dithranol 24 h after initial exposure to the drug. For protein content of attached cells the IC50 proved to be greater than 3.0 microM. Using 0.3, 1.0 and 3.0 microM dithranol, significant (p less than 0.05) dose dependent LDH release of 0.866 +/- 0.387, 1.842 +/- 1.127 and 2.938 +/- 1.635 mU per hour and cm2 confluent culture area was measured between the 5th and the 24th hour, compared to an acetone control of 0.504 +/- 0.299 mU/h x cm2. Between the 2nd and the 4th hour as well as from the 25th to the 48th hour and the 49th to the 72nd hour the LDH release after dithranol treatment did not exceed the control value. In accordance with these findings dose-dependent morphological signs of cell injury were detected by phase contrast microscopy beyond the 4th hour. The data reveal that: HaCaT cells are a very sensitive target for the antiproliferative action of dithranol; the drug causes considerable plasma membrane damage even at concentrations as low as 0.3 microM; and this membrane damage becomes evident after a latency of at least 4 h and for a limited period of up to 24 h.

Anthralin↗
PubMed1988

Keratinocyte grafting: a new means of transplantation for full-thickness wounds.

Twenty adult individuals with chronic leg ulcers caused by venous insufficiency, and 5 patients with full-thickness burns were treated. Twenty of the patients (15 with leg ulcers and 5 with burns) were grafted with separated autologous keratinocytes. In these cases the cells were fixed to the wound bed by a fibrin net. Five other patients (with leg ulcers) were treated with fibrin without keratinocytes. In 16 of the 20 patients grafted with keratinocytes in a fibrin net, the defect healed completely in 14 to 21 days. On the other hand, the fibrin net without keratinocytes failed to significantly accelerate the process of reepithelialization. Our experience suggests that a rapid healing of full-thickness skin defects can be achieved through keratinocyte grafting.

Burns↗