PL 14736 is a synthetic peptide, originally isolated from human gastric juice, that has anti-inflammatory and tissue-protective actions in experimental models of gastrointestinal inflammation. To investigate its possible benefit in poorly healing skin wounds, the effects of the topical application of PL 14736 in a gel formulation have been studied on full-thickness excisional wounds in rats, either healthy or made hyperglycemic by alloxan (175 mg/kg s.c.) 5 days previously. The effects of becaplermin gel (platelet-derived growth factor, PDGF-BB, Regranex^®), a standard therapy for diabetic foot ulcers, were investigated for comparison. Healing was evaluated for up to 7 days after wounding, using digital planimetry analysis, macroscopic scoring and histology. While healing was too rapid in healthy rats to observe enhancement by either treatment, in the hyperglycemic rats which exhibited delayed healing, PL 14736 (10–1,000 µg/wound) produced a dose-dependent acceleration of wound healing (determined by macroscopic scoring) equivalent at the highest doses to that observed with becaplermin. The beneficial effect on healing was associated with increased deposition of organized granulation tissue by day 7 for both PL 14736 and becaplermin, as determined histologically. PL 14736 tended to have a greater effect than becaplermin on the formation of granulation tissue containing mature collagen. Wound contraction, as measured by planimetry, was not significantly affected. In conclusion, topical PL 14736 produces a dose-dependent acceleration of deficient skin wound healing in hyperglycemic rats by facilitating granulation tissue formation, similar to the response seen with topical becaplermin, the standard therapy for diabetic skin wounds. PL 14736 may represent an alternative therapy for delayed wound healing, such as that seen with diabetic foot ulcers, without the proliferative concerns or immunogenicity associated with growth factors.

No abstract

The influence of dietary zinc originating from either inorganic or organic source on zincdepleted pigs was investigated. Within the 30 d period preceding the trial. all the animals (German Landrace x Pietrain x Large White x Swedish Landrace weaned crossbreds) were depleted of zinc and divided into three groups. 14 animals in each. During the experimental fattening period (105 d). the control group received no extra zinc. whereas the two trial groups were fed a diet with zinc supplement either as inorganic salt (ZnS0 4 ) or metalo-organic chelate (zinc methionate). On average. the respective supplements contained 84.3 mg Zn.kg· l diet and 40.9 mg Zn.kg-l diet.Evaluation of the nutritional effects of zinc was based on its concentration in the blood serum, bone and hair. Moreover. the effect of zinc on catalytical activity of alkaline phosphatase. aspartate aminotransferase. alanine aminotransferase and gamma-glutamyltransferase in serum was studied. A decrease of catalytical activity of both aspartate aminotransferase and alanine aminotransferase was found along with signs of parakeratosis on the skin of control animals but no correlation with serum zinc was established. In contrast to this finding. a linear correlation between catalytical activity of alkaline phosphatase and of gamma-glutamyltransferase and serum zinc level was found with the respective correlation coefficients of 0.90 and -0.72.Nutritional efficiency of diet zinc was evidenced by both higher (P < 0.05) zinc level in blood serum. bone and hair and by the state of hepatobiliary tract and bones. and favourable performance results of trial animals compared to controls. None of trial animals suffered from any health disturbances. Progressive parakeratosis appeared. however. in control animals and lasted during the second month of the trial. It was accompanied by deterioration of performance data of the affected animals.Our data suggest that bioavailability of zinc from the chelate was better than of that derived from inorganic salt. particularly in the period of rapid growth. This presumbaly resulted in reduced elimination of zinc. Based on better nutritional efficiency in pigs and on ecological benefits. zinc methionate should be preferred to ZnS0 4 as a zinc containing diet additive.Growth, pigs. ~illc sulphate. ~illc methionate. bioavailability, nutrition

bAs we face an alarming increase in bacterial resistance to current antibacterial chemotherapeutics, expanding the available therapeutic arsenal in the fight against resistant bacterial pathogens causing respiratory tract infections is of high importance. The antibacterial potency of macrolones, a novel class of macrolide antibiotics, against key respiratory pathogens was evaluated in vitro and in vivo. MIC values against Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, and Haemophilus influenzae strains sensitive to macrolide antibiotics and with defined macrolide resistance mechanisms were determined. The propensity of macrolones to induce the expression of inducible erm genes was tested by the triple-disk method and incubation in the presence of subinhibitory concentrations of compounds. In vivo efficacy was assessed in a murine model of S. pneumoniae-induced pneumonia, and pharmacokinetic (PK) profiles in mice were determined. The in vitro antibacterial profiles of macrolones were superior to those of marketed macrolide antibiotics, including the ketolide telithromycin, and the compounds did not induce the expression of inducible erm genes. They acted as typical protein synthesis inhibitors in an Escherichia coli transcription/translation assay. Macrolones were characterized by low to moderate systemic clearance, a large volume of distribution, a long half-life, and low oral bioavailability. They were highly efficacious in a murine model of pneumonia after intraperitoneal application even against an S. pneumoniae strain with constitutive resistance to macrolide-lincosamide-streptogramin B antibiotics. Macrolones are the class of macrolide antibiotics with an outstanding antibacterial profile and reasonable PK parameters resulting in good in vivo efficacy.

Vrandic N., L. Rupic, V. Ba(!ar-Huskic, S. Bogdan, M. Dominis-Kramaric: Influence of Multienzyme Preparations on Production Results and on Selected BiochemicalIndicators in the Blood of Pigs from 10 to 24 kg Body Mass. Acta vet. Bmo 1995,64: 235-242. Nutritional effects of two multienzyme preparations (PLIV A and Kemzyme) on the production and selected biochemical parameters in the blood of pigs weighing between 9.8 and 24 kg were studied during a period of 28 days. Yorkshire and Swedish Landrace crossbreds of 9.8 kg starting body mass were used. A total of 54 pigs were divided in three groups, a control (C) and two trial (TI and T2 ) groups with 18 pigs (9 males and 9 females) in each. They were fed the same starter diet. The control group received no enzyme supplement while the first group (TI) received the multienzyme preparation made by PLIVA and the second group (T2) was given a multienzyme preparation, Kemzyme (Kemin, Iowa, USA). Both diets (TI and T2) contained 0.1% of the multienzyme preparations. Pigs were kept in boxes and offered water and feed ad libitum. Nutritional parameters were measured at the end of the trial (after 28 days), while blood plasma biochemical parameters were ascertained on days I, 14 and 28. Pigs in the control group (C) and in both trial groups (T I and T 2) reached comparable average daily gains and average finishing body mass within the 28 days under study. The control group (e) consumed 10.9% more feed than the group T I (PLIV A multienzyme preparation), and 4.53% more feed than the groupT 2 (Kemzyme) during the 28 trial days. Both experimental groups fed diets enriched with multienzyme additives PLIV A or Kemzyme, had better food conversion than the control (C) group. No adverse effects of multienzyme preparations by PLIV A or Kemzyme on health status of pigs was found as indicated by biochemical analyses. Neither death nor sickness occurred during the trial. Nutrition, blood plasma, protein, lipid, glucose, AST, ALT, enzyme additivesAlthough research of the effect of different enzyme additions to the feed of domestic animals started in the 1960's, many questions have not been answered and many problems have not been solved yet. Enzymes used in animal feed are mostly of bacterial (genus Bacillus) or fungal (genuses Aspergillus, Trichoderma, Penicillium) origin (In borr 1989). Although enzymes are of various origin, molecular weight and amino acid sequences, they have similar effects on the digestive tract of animals. Enzyme activities depend on environmental conditions such as pH, temperature, activating substrate, inhibitors, and other factors that induce chemical reactions in the digestive tract. The effect of the addition of enzymes to animal feed is tightly connected to the species and age of animal, to the meal composition, and to the kind and number of enzymes in certain enzyme preparation. Trial results confirmed that the nutritive effect of enzymatic preparations is greater in young animals in which the entire enzyme system of digestive tract is not fully ...