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Biomedical subjects

M Tendler

Publications and source records attributed to M Tendler.

At least 19 recordsLinked to original sources

Pilot study of a novel treatment for androgenetic alopecia using enriched cell culture medium: clinical trials.

Androgenetic Alopecia (AA) afflicts a large part of the population and of the many treatments available today none is completely satisfactory. Testing the efficacy and safety of a novel topical treatment for AA which is based on cell culture medium supplemented with insulin, thyroxin and growth hormone (CCM). The 48 participants classified as androgenetic alopecia Type II, III or IV on the Hamilton scale, concluded a randomized, vehicle-controlled, double-blind trial of 6 months duration. Under occlusive cover the gel was self applied for at least 3 hours daily. Evaluation was based on hair counts, investigator global assessment and participants self-administered questionnaire. Cessation of hair loss was reported by most participants within 28 weeks, and further confirmed by the hair count (HC) in ~80% of participants. Moreover, as early as 4 months after the start of the treatment, a time dependent increase of up to 50% in HC was observed. The average change in HC between the two groups differed significantly (p=0.007), with values of 4.1% for control and 13.8% for CCM. Following 4 months of treatment, a time dependent increase in HC (>10%) above minimal was observed in 55% of the CCM and 25% of the control and this trend continued. At 6 months 63% of the CCM and 33% of the control group exhibited increase of HC higher than 10%. The average increase in HC in the CCM and the control groups was 17.1% and 8.9% respectively (p=0.035). Self evaluation questionnaires revealed a time dependent increase in satisfaction in the CCMusers compared to the control. While the average score at T2 was similar in CCM and control (2.7 and 2.6 respectively), the score at T6 in the CCM increased to 5.9 and decreased to -0.4 in the control (p=0.007). Global-clinical evaluation following six months treatment revealed significantly (p=0.02) more hair loss in the control group (40%) compared to the CCM (7%) treated group. CCM was found effective in treating androgenetic alopecia in men. It induced cessation of hair loss, increased rate of hair growth and appearance of new hair. No side effects were reported or observed.

Administration, Topical↗

Preliminary analysis of Sm14 in distinct fractions of Schistosoma mansoni adult worm extract.

In previous studies it was shown that the recombinant molecule, r-Sm14, induces high levels of protection against Schistosoma mansoni infection in two outbred animal models and immune crossprotection against infection by Fasciola hepatica in Swiss outbred mice. r-Sm14 was derived from a living worm extract, called SE, and is being developed as the molecular basis of an anti-helminth bivalent vaccine against the two parasites, for medical and veterinary application. Present data refer to SDS-PAGE and Western Blotting analysis of four different preparations of S. mansoni adult worms focusing Sm14 identification. The extracts correspond to the initial fraction of the SE extraction process, containing products released by living worms (SEi); SE2, reextraction of adult worms in PBS; and SE of separated male and female adult worms. In all extracts it was possible to detect the component of 14 kDa, that was recognized by specific anti-rSm14 antibody raised in rabbits.

Animals↗

r-Sm14 - pRSETA efficacy in experimental animals.

Previous studies carried out with Sm14 in experimental vaccination against Schistosoma mansoni or Fasciola hepatica infections were performed with recombinant Sm14 (rSm14) produced in Escherichia coli by the pGEMEX system (Promega). The rSm14 was expressed as a 40 kDa fusion protein with the major bacteriophage T7 capsid protein. Vaccination experiments with this rSm14 in animal models resulted in consistent high protective activity against S. mansoni cercariae challenge and enabled rSm14 to be included among the vaccine antigens endorsed by the World Health Organization for phase I/II clinical trials. Since the preparation of pGEMEX based rSm14 is time consuming and results in low yield for large scale production, we have tested other E. coli expression systems which would be more suitable for scale up and downstream processing. We expressed two different 6XHis-tagged Sm14 fusion proteins in a T7 promoter based plasmids. The 6XHis-tag fusions allowed rapid purification of the recombinant proteins through a Ni+2-charged resin. The resulted recombinant 18 and 16 kDa proteins were recognized by anti-Sm14 antibodies and also by antiserum against adult S. mansoni soluble secreted/excreted proteins in Western-Blot. Both proteins were also protective against S. mansoni cercariae infection to the same extent as the rSm14 expressed by the pGEMEX system.

Animals↗

Relativistic plasma viscosity of the Burnett kind.

Hydrodynamic equations to describe relativistic and ultrarelativistic plasma dynamics were obtained by Dzhavakhishvili and Tsintsadze [Sov. Phys. JETP 37, 666 (1973)] using the Chapman and Enskog scheme to solve the relativistic kinetic equations for the different plasma species. This approach leads to a representation of the particle viscosities in the Navier-Stokes form and, therefore, some relevant physical processes, such as the Burnett type of particle viscosity, cannot be properly dealt with in this scheme. In this paper we employ the extended Grad method to derive hydrodynamic equations which include ultrarelativistic viscosities of the Burnett type, i.e., viscosities that depend not only on derivatives of the particle macroscopic velocities but also on derivatives of particle heat fluxes.

Journal Article↗

Improved vitality of experimental random dorsal skin flaps in rats treated with enriched cell culture medium.

A defined, serum-free cell culture medium supplemented with nonsteroidal anabolic hormones, insulin, thyroxin, and growth hormone was found to accelerate wound healing by stimulating vascularized granulation tissue formation, epithelialization, and angiogenesis. The aim of this work was to study the effect of cell culture medium on the survival rate of cephalically based random dorsal skin flaps in an animal model. A total of 77 Sprague-Dawley rats were randomized into five treatment groups: pharmacologic delay with cell culture medium, flap enhancement with cell culture medium, surgical delay, biological delay with saline, and control. Statistically significant differences in distal flap necrosis were found among all groups (p<0.003). The rats treated with cell culture medium before flap elevation showed a significant increase in flap viability: a survival rate of 83 percent, compared with the control group, which demonstrated a survival rate of only 58 percent (p<0.0001). The surgical delay and the groups treated with cell culture medium yielded similar results with no significant difference between them. This study indicates that preoperative injection of cell culture medium may play a role in decreasing skin flap necrosis.

Animals↗

Static-electric field induction by a silicone cushion for the treatment of hypertrophic and keloid scars.

Silicone gel and silicone occlusive sheeting are widely used at present for the treatment of hypertrophic and keloid scars, without any scientific explanation as to their mode of action. In a recent paper the possibility was raised that static electricity generated by friction-activated silicone sheeting could be the reason for this effect, and that it can, with time, cause involution of hypertrophic and keloid scars. The objective of this study was to test this hypothesis and to observe whether a continuous and also an increased negatively charged static-electric field will shorten the treatment period. A device to implement these requirements gradually evolved over a 5-year period. A number of prototypes were tested until the final product was attained. Some of the patients in this study were treated initially with a silicone sponge inserted in the cushion. Later this version was changed to the final design described herein. A silicone cushion was developed with the purpose of increasing a negative static-electric charge to accelerate the regression process. The cushion is custom-made using a silicone occlusive sheeting envelope of 0.75-mm thickness, which does not deteriorate with use, and is partially filled with high viscosity silicone oil. Its edges are sealed, and its size is designed to extend a little beyond the scarred area. Static electricity readings, generated by activating the cushion by pumping action with the fingers, stretching or deforming the cushion, are invariably much higher when compared with those obtained with silicone occlusive sheeting and silicone gel sheeting. The interaction between the negatively charged ions of the cushion and the ionic charges of the tissue fluids may be the critical factor in achieving hypertrophic and keloid scars involution. Of the 30 patients enrolled in the study, 3 patients dropped out. Treatment with the silicone cushions yielded 63.3 percent cessation of itching and burning followed by pallor and flattening of the scar, some markedly so, over a few weeks to 6-month period. An additional 26.6 percent had their scars resolved in up to 12 months of treatment. Good contact of the cushion over the scar has been shown to be important in this clinical trial, and much creativity is needed for making elastic strap bindings that ensure this contact. The clinical trials extended over a 12-month period. Ten patients (33.3 percent) who had recalcitrant scars with little response to the use of the silicone cushion were given intralesional corticosteroid injections, in addition to the continued use of the cushion, resulting in a fairly rapid resolution of these scars over a period of months to a year.

Adolescent↗

A Schistosoma mansoni fatty acid-binding protein, Sm14, is the potential basis of a dual-purpose anti-helminth vaccine.

Molecular cloning of components of protective antigenic preparations has suggested that related parasite fatty acid-binding proteins could form the basis of the protective immune crossreactivity between the parasitic trematode worms Fasciola hepatica and Schistosoma mansoni. Molecular models of the two parasite proteins showed that both molecules adopt the same basic three-dimensional structure, consisting of a barrel-shaped molecule formed by 10 antiparallel beta-pleated strands joined by short loops, and revealed the likely presence of crossreactive, discontinuous epitopes principally derived from amino acids in the C-terminal portions of the molecules. A recombinant form of the S. mansoni antigen, rSm14, protected outbred Swiss mice by up to 67% against challenge with S. mansoni cercariae in the absence of adjuvant and without provoking any observable autoimmune response. The same antigen also provided complete protection against challenge with F. hepatica metacercariae in the same animal model. The results suggest that it may be possible to produce a single vaccine that would be effective against at least two parasites, F. hepatica and S. mansoni, of veterinary and human importance, respectively.

Amino Acid Sequence↗

Serum-free cell culture medium induces acceleration of wound healing in guinea-pigs.

Among the current methods employed in the treatment of wounds, a moist dressing is considered to be the optimal environment for the process of healing thereby avoiding dessication of the wound bed. This study is based on the hypothesis that wound cell proliferation is dependent not only on moisture but also upon the composition of the moist microenvironment in the wound. That composition in turn is formed by diffusion of nutrients from the existing vascular bed in and around the wound as well as by the wound cells' cellular products. Since in wounds the impaired vascular supply causes tissue deprivation, a continuous supply of nutrients and hormones will create an optimal substrate for cellular mitogenic activity, synthesis of matrix, growth factors and cytokines leading to wound healing. Modified serum-free cell culture medium was supplemented with non-steroidal anabolic hormones: growth hormone, thyroxin and insulin, transferrin and sodium selenite. The medium was prepared in a 1 per cent alginate gel matrix. Under general anaesthesia with ketamine (Imalgene 1000, Rhone Merieux, France) four 2 x 2 cm full-thickness skin patches were surgically extirpated from the dorsum of Hartley-derived guinea-pigs. Each experimental group consisted of seven animals, i.e. 28 wounds that received the same treatment. Compositions of gelatin in saline, agarose in saline, agarose in medium and agarose in saline supplemented with the three hormones were compared to agarose in medium supplemented with the three hormones. After application of the gel (1 ml/cm2), the wounds were dressed with gauze, elastic adhesive bandage and netting.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Immunoreactivity of a cytokeratin-related polypeptide from adult Schistosoma mansoni.

A saline extract (SE) derived from living adult Schistosoma mansoni confers high levels of resistance to challenge infection in mice and rabbits. We have carried out a number of experiments to analyse the composition of SE and to define the proteins that are rapidly released from the parasite. One of these proteins, with apparent molecular mass of 62 kDa, is recognized by polyclonal and monoclonal antibodies raised against high molecular mass cytokeratins from human epidermal cells. Immunocytochemical studies revealed a tegumental staining using the anti-cytokeratin antibody. Moreover, sera from schistosomiasis patients, as well as those from animals immunized with SE, were able to recognize this 62 kDa polypeptide as shown by immunoblot assays. These results suggest the existence of cytokeratin-containing filaments in the schistosome.

Animals↗

Vaccination in murine schistosomiasis with adult worm derived antigens--II. Protective and immune response in inbred mice.

Previous work in our laboratory, mainly focused the prospects of achieving resistance against Schistosoma mansoni infection with adult worm-derived antigens in the form of a soluble extract (SE). This extract obtained by incubation of living adult schistosomes in saline, contains a large number of distinct molecules and was actually shown to be significantly protective in different outbred animals models such as Swiss mice and rabbits. It thus appeared worthwhile to investigate the potential protective activity of SE in different inbred strains of mice, known to be highly susceptible to the infection. Herein we present data showing that DBA/2 mice, once immunized with SE acquire significant levels of resistance to a S. mansoni cercarial challenge. In addition, preliminary studies on the immune system of immunized animals revealed that, injection of SE caused no general imbalance of B or T cell responses.

Animals↗

A 14-kDa Schistosoma mansoni polypeptide is homologous to a gene family of fatty acid binding proteins.

The complete nucleotide sequence encoding a Schistosoma mansoni protein termed Sm14 was determined from cDNA clones propagated in bacteriophage lambda gt11 in Escherichia coli. The 14.8-kDa protein bears significant homologies with a family of related polypeptides which bind hydrophobic ligands. Members of this group of cytosolic proteins were originally identified based on their affinity for long chain fatty acids. The purified recombinant protein exhibited an affinity to fatty acids, in contrast to a mutant lacking 16 N-terminal amino acids. Immunofluorescence experiments show that tubercles, which are structures located on the dorsal surface of adult male schistosome and known to contain lipids, are stained using antibodies raised to the beta-galactosidase fusion protein. A regular staining pattern is also evident in the muscle layers as well as in the body of the parasite. As the schistosome cannot synthesize fatty acids de novo and is dependent on the uptake of lipids from serum, the available data support a role for Sm14 in the transport of fatty acids.

Animals↗

Vaccination in murine schistosomiasis with adult worm-derived antigens: variables influencing protection in outbred mice.

Previous studies have shown that both permissive (mouse) and partially permissive (rabbit) hosts develop high levels of resistance against Schistosoma mansoni infection after vaccination with a multiple antigen extract (SE) obtained by incubation of living adult worms in saline, plus bacterial adjuvant. To investigate variables influencing SE-induced protection in murine schistosomiasis, a series of distinct vaccination protocols were performed focussing on the immunization dose, carrier systems, route, site and amplitude of challenge infection, and time between immunization and challenge. In addition, a new approach was adopted to evaluate SE protective activity, by means of population analysis of worm burden frequency distributions in a large scale study of vaccination in outbred Swiss mice. Distinct curves of frequency and a drastic difference in worm burden distribution of frequencies from SE-vaccinated x non-vaccinated mice were found. It was shown that SE could generate 75% mean protection in outbred mice even in the absence of adjuvant. In addition SE immunization was also able to induce full protection against lethal infection. SE-induced protection could be modulated by such parameters as dose of SE immunization/challenge interval, and route of cercariae injection. These data show that SE yields very high protective activity in outbred mice, and may provide a further insight for rational design of a vaccine in experimental schistosomiasis.

Animals↗

Schistosoma mansoni-New Zealand rabbit model: resistance induced by infection followed by active immunization with protective antigens.

In previous studies, rabbits immunized with adult worm antigens released from fresh adult schistosomes incubated in saline media showed a significant level of protection against challenge parasites. Focusing on the rabbit-Schistosoma mansoni model, concomitant immunity was investigated. A peculiar form of response to cercarial infection was observed: rabbits subjected to percutaneous infection and similar reinfections at different times after primary infection killed schistosomula from the challenge infection as well as established parasites from the primary infection. In this study the challenge infection stimulus was replaced by active immunization with an adult worm-derived protective antigenic mixture. The results show that immunization of New Zealand rabbits with an adult worm antigenic extract is capable of inducing a response that results in a significant reduction of the mean worm burden of the primary infection earlier than did homologous infection, as compared to worm reduction due to a second infection.

Animals↗

The diagnosis of bacteriuria during pregnancy.

Three diagnostic tests, Nitur, Urobact, and Uricult, were evaluated in the detection of bacteriuria in 865 pregnant women. As reference method agar culture was performed. Heavy growth (greater than 10(5) CFU/ml) of urinary tract bacteria was considered a true positive result and demonstrated in 58 (6.7%) of the women, 14 of whom had gram-negative rods. The sensitivity of the nitrite test was extremely low (0.13). The test gave negative results in eight of 17 specimens yielding heavy growth of Escherichia coli or Proteus mirabilis. Although the Urobact test was highly sensitive as regards gram-negative infection, it had an unacceptably low (0.27) predictive value in positive tests. The sensitivity of the Uricult test was low (0.35) in this study. The predictive value (0.50) of a positive test result may be acceptable, since just over half of the false positive results were explainable by moderate growth of urinary tract pathogens (10(4)-10(5) CFU/ml). It is argued that semi-quantitative urine culture may be preferable to the rapid diagnostic methods studied for the screening of bacteriuria in pregnant women.

Agar↗

Curative and protective activity in rabbits after reinfection with Schistosoma mansoni: a new model of immunity?

New Zealand rabbits were infected on day 1 and challenged on days 15, 30, and 60 with 1,000 Schistosoma mansoni cercariae/animal/infection. Challenged and control rabbits were perfused 60 days after each infection, corresponding to days 75, 90, and 120 after the first exposure. No decrease in number of adult schistosomes occurred in animals reinfected 15 days after primary infection, but, when the rabbits were challenged 30 and 60 days after the first infection, worm burden reduction of 61.4% and 92.6%, respectively, was observed as compared to infection controls. These data indicate that rabbits submitted to reinfection are able to kill the worms from their primary infection, besides being protected against challenge parasites.

Animals↗