Honey, bee pollen and vegetable oil unsaponifiables in wound healing.

We would like to remark on the mechanisms and therapeutic properties of honey, bee pollen and unsaponifiable fractions of vegetable oils in wound healing.

Cardiorenal consequences of atherosclerosis and statins therapy: from the past to the future.

Complications from atherosclerosis cause most deaths in western countries, and their incidence appears to be markedly increasing in developing countries, thus suggesting a correlation that is directly proportional to social progress. In recent years, the different branches of medical research, from studies on vascular disease to those on lipid and glucose metabolism, and also clinical research on coronary, carotid and peripheral artery diseases, epidemiologic and pharmacologic research, have concentrated on these diseases with the common aim of reducing the incidence of cardiovascular diseases, and mortality. Scientific progress has greatly improved our understanding of the pathogenic mechanisms underlying the progression of cardiovascular disease, and efforts in this discipline now appear more necessary than ever.

Osteoprotegerin, IL-6, IL-1, TNF-alpha and TGF-beta concentrations during acetate-free biofiltration.

To ascertain the effect of acetate-free biofiltration (AFB), performed with polyacrilonitrile filters, on serum concentrations of osteoprotegerin (OPG) and other bone-acting cytokines (interleukin (IL) IL-1, IL-6, tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta)) in end-stage renal disease (ESRD) patients, we evaluated these parameters during an AFB session and 24 hr after it ended. In second time we verified the existence of eventual correlations among serum levels of all these cytokines at different times. We investigated 48 subjects: 24 healthy volunteers (controls) (12 females, 12 males, mean age 55 +/- 9 yrs) and 24 ESRD patients (12 females, 12 males, mean age 58 +/- 6.7 yrs, mean dialytic age 2.7 +/- 1.6 yrs, residual glomerular filtration rate (GFR) 2.3 +/- 0.6 ml/min). All dialyzed patients received regular AFB with polyacrilonitrile filters for 4 hr thrice-weekly. Statistical analysis showed significant increase in basal serum OPG, IL-6 and TNF-alpha concentrations in dialyzed patients compared to controls, while it did not show significant variations for the other cytokines. During the dialytic session, OPG and TGF-beta concentrations did not show significant variations, while serum TNF-alpha, IL-6 and IL-1 levels significantly decreased from the 1st hour of AFB. None of the cytokines showed significant differences between basal and interdialytic values. We did not find correlations between OPG, IL-1, IL-6, TNF-alpha and TGF-beta concentrations during hemodialytic sessions and during the interdialytic interval. It is our opinion that the lack of correlation between serum concentrations, observed in our study, could not exclude the presence of local interferences between OPG and the other cytokines.

Brain and cancer: the protective role of erythropoietin.

Erythropoietin (Epo) is a pleiotropic agent, that is to say, it can act on several cell types in different ways. An independent system Epo/Epo receptor (EpoR) was detected in brain, leading to the hypothesis that this hormone could be involved in cerebral functions. Epo/EpoR expression changes during ontogenesis, thus indicating the importance of this system in neurodevelopment. Moreover, the hypoxia-induced production of Epo in the adult brain suggests that it could exert a neurotrophic and neuroprotective effect in case of brain injury. Epo could also influence neurotransmission, inducing neurotransmitters (NT) release. Epo therapy in anemic cancer patients is still a controversial issue, because of its possible action as a growth and an angiogenic factor. In our speculative hypothesis Epo could be involved in a "two steps process" that, after a neovascularization phase, leads to its down regulation. Moreover, Epo-activated signaling pathways could be modulated as possible targets to interfere in neoplastic cells cycle. In conclusion, treatment with rHuEpo could change therapeutical perspectives in different pathological conditions, such as central nervous system (CNS) diseases, but further studies are needed to clarify its physiopathological activities in different clinical fields.

Aquaporin-2 water channels in spontaneously hypertensive rats.

Vasopressin (AVP), an antidiuretic hormone, is known to induce hypervolemia and to regulate the renal expression of aquaporin-2 (AQP2) water channels, but it is not yet known whether the latter are involved in the pathogenesis of essential hypertension. The aim of the present study was therefore to make a comparative study of blood pressure (BP), urinary volume (UV), urinary osmolarity (uOsm), urinary AQP2 (uAQP2), and plasma AVP levels (PAVP) in male spontaneously hypertensive rats (SHR; n = 30) at 3, 7, and 12 weeks of age and in male Wistar-Kyoto rats (WKY, n = 30), also after the subcutaneous administration of OPC-31260 (OPC), a human AVP V(2) receptor antagonist. At 3 weeks, SHR had markedly higher uOsm and lower UV levels than WKY. At 7 weeks, SHR were hypertensive, showing increased uAQP2, PAVP, and uOsm levels and a decreased UV. At 12 weeks, no significant changes were observed in this condition. At 7 and 12 weeks of age, OPC-treated WKY rats showed significant reduction in BP and uOsm and increase in UV with respect to untreated animals. From 3 weeks of age, OPC-treated SHR presented significantly lower BP levels, higher UV levels, and lower uOsm than untreated animals. In treated WKY and SHR, uAQP2 levels were lower than in untreated animals. The PAVP appeared to be higher in OPC-treated rats from both strains. These findings suggest that AVP and the AQP2 are involved in the pathogenesis of hypertension in SHR.

Angiotensin-converting enzyme and angiotensin type 2 receptor gene genotype distributions in Italian children with congenital uropathies.

Angiotensin I-converting enzyme (ACE) and angiotensin type 2 receptor (AT2R) gene polymorphisms have been associated with an increased incidence of congenital anomalies of the kidney and urinary tract (CAKUT). We investigated the genotype distribution of these polymorphisms in Italian children with CAKUT. We also evaluated the association between the ACE insertion/deletion and the AT2R gene polymorphisms with the progression of renal damage in subgroups of CAKUT patients. We recruited 102 Italian children with CAKUT; 27 with vesicoureteral reflux; 12 with hypoplastic kidneys; 20 with multicystic dysplastic kidneys; 13 with ureteropelvic junctions stenosis/atresia; 18 with nonobstructed, nonrefluxing primary megaureters; and 12 with posterior urethral valves and compared them with 92 healthy control subjects. ACE and AT2R gene polymorphisms were analyzed by PCR. The identification of AT2R gene polymorphisms in intron 1 and in exon 3 was revealed by enzymatic digestion. ACE genotype distribution in children with CAKUT was no different from that of the control subjects, but the subgroup of patients with radiographic renal parenchymal abnormalities showed an increased occurrence of the D/D genotype. The frequency of the G allele of AT2R gene in children with CAKUT was increased in respect to that of the control subjects. By contrast, no significant difference in the frequency of the C and A alleles of the AT2R gene was found. Our findings indicate that the ACE gene can be a risk factor in the progression of renal parenchymal damage in CAKUT patients. Moreover, a major role of the AT2R gene in the development of CAKUT has been found, at least in Italian children.

Vasectomy reversal and spermatic granuloma: experimental investigation.

The aim of our study was to investigate the healing process after vasectomy reversal, comparing two suturing techniques. Eighty Wistar rats received a two-layer vaso-vasostomy on the right side, and 40 of them also received a single-layer vaso-vasostomy on the left side. Twenty rats each time were sacrificed at 30, 45, 60, and 90 days. Results were evaluated in order to compare the two techniques used and to describe the progression of healing, with special reference to anastomotic patency rate, histologic aspect of the epididymus and testicle, and the presence and size of spermatic granuloma. We observed 45% patency with the double-layer technique compared to 20% with the single-layer technique. The testicle appeared atrophic in 20% of double-layer cases compared to 40% of single-layer cases. Comparison over time showed a progressive increase in patency of the anastomosis, reduction of spermatic granuloma, and regression of testicular damage. Our results show the superiority of the double-layer technique, and contribute to an understanding of the role of two different suturing techniques in the outcome of vasectomy reversal.

Recombinant human erythropoietin (rHuEPO): more than just the correction of uremic anemia.

Hematopoiesis is controlled by numerous interdependent humoral and endocrine factors. Erythropoietin (EPO), a hydrophobic sialoglycoproteic hormone, plays a crucial role in the regulation of hematopoiesis, and induces proliferation, maturation and differentiation of the erythroid cell line precursors. Thanks to recombinant DNA techniques, different recombinant hormones can now be produced at low cost and in large amounts. This has led to greater understanding of the pathophysiological factors regulating hematopoiesis. This in turn, hasprompted the search for new therapeutic approaches. EPO might also be used to treat patients with different types of anemia: uremics, newborns, patients with anemia from cancer or myeloproliferative disease, thalassemia, bone marrow transplants, chronic infectious diseases. Besides erythroid cells, EPO affects other blood cell lines, such as myeloid cells, lymphocytes and megakaryocytes. It can also enhance polymorphonuclear cell phagocytosis and reduce macrophage activation, thus modulating the inflammatory process. Hematopoietic and endothelial cells probably have the same origin, and the discovery of eyrthropoietin receptors also on mesangial, myocardial and smooth muscle cells has prompted research into the non-erythropoietic function of the hormone. EPO has an important, direct, hemodynamic and vasoactive effect, which does not depend only on an increase in hematocrit and viscosity. Moreover, EPO and its receptors have been found in the brain, suggesting a role in preventing neuronal death. Finally, the recently discovered interaction between EPO and vascular endothelial growth factor (VEGF), and the ability of EPO to stimulate endothelial cell mitosis and motility may be of importance in neovascularization and wound healing.

Statins and progressive renal disease.

Thanks to the administration of hypocholesterolemic drugs, important advances have been made in the treatment of patients with progressive renal disease. In vitro and in vivo findings demonstrate that statins, the inhibitors of HMG-CoA reductase, can provide protection against kidney diseases characterized by inflammation and/or enhanced proliferation of epithelial cells occurring in rapidly progressive glomerulonephritis, or by increased proliferation of mesangial cells occurring in IgA nephropathy. Many of the beneficial effects obtained occur independent of reduced cholesterol levels because statins can directly inhibit the proliferation of different cell types (e.g., mesangial, renal tubular, and vascular smooth muscle cells), and can also modulate the inflammatory response, thus inhibiting macrophage recruitment and activation, as well as fibrosis. The mechanisms underlying the action of statins are not yet well understood, although recent data in the literature indicate that they can directly affect the proliferation/apoptosis balance, the down-regulation of inflammatory chemokines, and the cytogenic messages mediated by the GTPases Ras superfamily. Therefore, as well as reducing serum lipids, statins and other lipid-lowering agents may directly influence intracellular signaling pathways involved in the prenylation of low molecular weight proteins that play a crucial role in cell signal transduction and cell activation. Statins appear to have important potential in the treatment of progressive renal disease, although further studies are required to confirm this in humans.