Accelerated healing of excisional skin wounds by PL 14736 in alloxan-hyperglycemic rats.

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 microg/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.

Plasma proteins and haematological parameters in fattening pigs fed different sources of dietary zinc.

The effect of varying amounts of sources of dietary zinc on some blood parameters and the plasma protein ratios of fattening pigs was studied. During a 30-day pre-trial period, 42 pigs were depleted of Zn and divided into three groups of 14 animals each. During the 105-day experimental fattening period two experimental groups (T1-2) were repleted with dietary Zn in the form of inorganic salt (ZnSO4) or metallo-organic chelate (zinc methionate, ZnMET), while the control group (C) received no extra Zn. The supplements contained 84.3 and 40.9 mg Zn/kg diet, respectively. The nutritional effects of Zn were evaluated on the basis of red blood cell (RBC) count, mean corpuscular volume (MCV), haemoglobin (Hb) concentration, packed cell volume (PCV), white blood cell (WBC) and thrombocyte count, plasma total protein, albumin, and globulin concentrations, and albumin/globulin (A/G) ratio. During the parakeratosis period (days 28-56) both the basic feed (group C) and the diet enriched with 40.9 mg Zn/kg (as ZnMET) fed to group T2 pigs resulted in a lower red blood cell (RBC) count, Hb concentration and PCV than in group T1 fed a diet containing 84.3 mg Zn/kg (as ZnSO4). Dietary Zn of organic and inorganic origin had no effect on MCV and on the WBC and thrombocyte counts of fattening pigs. At the start of the parakeratosis period (day 28), group C pigs had significantly lower, and by its end (day 56) significantly higher plasma total protein and globulin concentrations than pigs of group T1. At the same time, no significant differences were observed in albumin concentration between group C and the two experimental groups. Throughout the trial, feed containing sufficient, and insufficient, quantities of Zn from various sources had no influence on blood plasma alpha and beta globulin concentrations. In the second part of the experiment (day 56) dietary Zn deficiency resulted in a significantly higher level of gamma globulin in group C pigs than in pigs given sufficient Zn of inorganic origin. While inorganic Zn increased some of the blood parameters, namely RBC count, Hb and possibly PCV, organic Zn seemed to be responsible for raising the proportion of plasma globulins.

Changes in skeletal metabolism in pubertal girls can be revealed by biochemical parameters of calcium metabolism and bone turnover.

Biochemical changes related to skeletal turnover in puberty were investigated in a sample of 67 girls aged 8-14 years. The following biochemical parameters were measured in serum: total calcium, phosphate, magnesium, total alkaline phosphatase, osteocalcin, and calcium and hydroxyproline in the second morning urine. Thirty-five premenarchal girls (8-11 years) had significantly lower serum calcium, and higher alkaline phosphatase and phosphate than those menstruating regularly (N = 32, 12-14 years). A statistically significant negative correlation of serum parameters and age was found for phosphate and alkaline phosphatase in all subjects, and for calcium and magnesium only in the premenarchal girls. These results indicated the more intensive processes of skeletal metabolism occurring in prepubertal age and early puberty to reflect in basic biochemical parameters of calcium and bone metabolism. Analysis of correlation between biochemical parameters showed alkaline phosphatase and phosphate to correlate positively with hydroxyproline excretion and negatively with urinary calcium in all subjects. In the subjects after menarche, osteocalcin correlated with alkaline phosphatase and phosphate. Thus, biochemical parameters indirectly reflected physiologic changes occurring with bone turnover in puberty. Variations in bone turnover during puberty, including a more pronounced bone formation during prepubertal or early stages, can be indirectly observed through biochemical parameters related to calcium and bone metabolism. Investigations of skeletal growth and puberty would benefit from specific markers of bone remodeling and "basic" biochemical parameters, as it might disclose subtle metabolic relationships.

Leukocyte alkaline phosphatase and serum gamma-glutamil transferase activities in horses used for production of hyper immune sera.

The activities of leukocyte alkaline phosphatase (l-AP) and serum gamma-glutamil transferase (gamma-GT), and total leukocyte counts were determined in horses submitted to the production of hyper immune sera against tetanus (Clostridium tetani). The purpose of this work was to investigate the prospective changes of mentioned parameters in horses under the described circumstances. In addition, the suitability of these parameters in assessing the health condition of the same horses had to be evaluated. The average total leukocyte count increased in one month from the values considered as physiological (8.8 x 10(9)/L, Schalm et al. 1975) to the value of 12 x 10(9)/L and remained at this level up to the end of the trial. The I-AP activities fell after 30 days of the trial for 100 units, and showed permanent slight decreasing tendency thereafter. On the contrary, the serum gamma-GT activity was increasing gradually throughout the whole trial. The results indicate the possibility of reflecting the dynamics of intensified leukocyte metabolism in the course of its function within the chronic inflammation, and development of accompanying pathological changes in the liver. In addition, the initialisation period of pathological changes in the organism of horses in experiment could be between the fourth and sixth month following exposure to antigen.