Olanzapine during lactation: impact on testicular morphometry and endocrine parameters in adult wistar rats.

Olanzapine (OLZ) is an antipsychotic medication used to treat postpartum psychiatric symptoms. It aimed to evaluate the effects of administering OLZ to lactating rats on testicular parameters of adult Wistar rats. Mothers received 2.5, 5 or 10 mg/kg until weaning. Adult male rats showed decrease in body weight, weight of testes, epididymis, prostate, seminal gland and gonadosomatic index when higher doses of OLZ were administered. Testicular volumetric parameters, as well as the length of seminiferous tubules, were also reduced in animals treated with the highest doses of OLZ. The diameter of the seminiferous tubules and the height of the seminiferous epithelium were reduced. There was also a relevant decrease in the population of Sertoli cells and a relevant reduction in the volume of individual Leydig cells. Histopathological analysis of the testes showed lesions compatible with testicular degeneration in rats treated with the highest dose of OLZ. There was a significant reduction in plasma testosterone levels in all treatments. It is noted, therefore, that the adverse impact on the testes of the highest doses of the drug during the neonatal period persisted into adulthood, with the dose of 2.5 mg/kg of OLZ proving to be safer than the others.

Supplementation of feedlot lambs with cactus cladodes as strategy to improve testicular function.

The aim of this study was to evaluate the effects of diets containing cactus cladodes genotypes on plasma testosterone levels, testicular histopathological and histomorphometric parameters, and oxidative stress markers in lambs. Thirty-six male, intact Santa Inês lambs (22.0 ± 2.9 kg initial body weight), were to feedlot for 86 days. A completely randomized design was used with three dietary treatments (control diet with Tifton-85 hay as the only roughage; and two more diets with Miúda or OEM cactus cladodes partially replacing hay) and twelve replicates. There was no influence of the diets on the testicular weight (P = 0.414) and gonadosomatic index (P = 0.384) of lambs. The testosterone serum concentrations were almost twice as higher in lambs fed Miúda cactus cladodes compared to control treatment. There was greater incidence and severity of lesions in the testicular parenchyma of animals that received control diet: loosening of germ cell epithelium, germ cell desquamation and vacuolization of Sertoli cells. The seminiferous tubule diameter and height of the seminiferous epithelium were higher in lambs fed OEM cactus cladodes (P = 0.003). The tubular volume and Leydig cells volume were higher in animals fed with cactus cladodes (P < 0.05). The levels of malondialdehyde were higher in the lambs of control group compared to OEM group (P = 0.039) and the testicular concentration of nitric oxide was higher in control group (P = 0.009). The diet containing OEM cactus cladodes increased the levels of superoxide dismutase. Our results indicate that diets containing cactus cladodes promote antioxidant protection to the testicular parenchyma and preserve the spermatogenic process of lambs.

Histomorphometric and oxidative evaluation of the offspring's testis from type 2 diabetic female rats treated with metformin and pentoxifylline.

Type 2 diabetes mellitus (T2D) during pregnancy is characterized by high levels of reactive oxygen species and pro-inflammatory factors in the placenta. Once these reactive species reach the foetus, they trigger physiological adaptations that allow the foetus to survive, but programme the organism to develop metabolic disorders in adulthood. The male reproductive system is highly susceptible to foetal programming. This study aimed to investigate the effects of intrauterine exposure to T2D on testicular histomorphometry and redox homeostasis of adult rats and evaluate the effects of maternal treatment with metformin and pentoxifylline. Female rats were induced to T2D, then treated with metformin and pentoxifylline, or co-treated with both drugs. The females were mated, the male offspring were sacrificed on postnatal day 90, and the testicles were collected for analysis. Metformin protected the tubular compartment, with the maintenance of the Sertoli cell population and daily sperm production. Pentoxifylline attenuated the effects of diabetes on Leydig cells, in addition to stimulating testosterone production and lowering lipid peroxidation. Intrauterine exposure to T2D results in important testicular alterations that compromise gonadal function, and the co-treatment with metformin and pentoxifylline may represent a promising therapy that attenuates these effects by combining the positive influences in both the tubular and interstitial compartments of the testicular parenchyma.

Antiinflammatory and antiinfective effect of caffeine in a mouse model of disseminated salmonellosis.

Caffeine has been reported for its antiinflammatory properties by stimulating phagocytosis. In this study, we investigated the antiinflammatory and antiinfective potential of caffeine in murine macrophage cell cultures and Swiss mice infected with virulent Salmonella enterica serotype typhimurium. Peritoneal macrophages (pMØ) were treated with caffeine on 96-well plates for 24 hr and then infected with Salmonella for 4 hr. In another experiment, the pMØ were first infected with the bacterium for 4 hr and then treated with caffeine for 24 hr. In addition, Swiss mice were inoculated, intraperitoneally, with S. typhimurium and then received caffeine intravenously. Control groups received phosphate-buffered saline (PBS) or dexamethasone. We found that treatments with caffeine increased the macrophage cell viability and reduced the intracellular bacterial load. The administration of caffeine to Swiss mice reduced the infiltration of leukocytes into the peritoneal cavity after the bacterial challenge. Furthermore, the bacterial burdens in the peritoneal fluid, bloodstream, spleen, and liver were decreased by caffeine treatment. The expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6, and inducible nitric oxide synthase (iNOs) were down-regulated after infection in caffeine-treated mice. We can conclude that caffeine has both antiinflammatory and antiinfective properties that can be useful for management of bacterial infections along with antibiotics.

Kidney changes in lambs fed cactus pear varieties resistant to Dactylopius opuntiae as the only roughage.

This study aimed to evaluate the effects of four varieties of cactus pear resistant to carmine cochineal as exclusive roughage for lambs on the biochemical, histopathological, and histomorphometric parameters of kidneys. Twenty-four castrated male crossbred lambs at eight months of age and an initial body weight of 21.0 ± 0.5 kg were distributed in a completely randomized design, with four treatments and six repetitions. The experimental treatments consisted of four diets containing Miúda cactus pear, IPA-Sertânia cactus pear, IPA-F21 cactus pear, or Orelha de Elefante Mexicana (OEM) cactus pear as the only roughage. Blood samples were collected every two weeks (14 d, 28 d, 42 d, and 56 d) to quantify serum urea and creatinine levels. After 72 days of the introduction of the tested diets, the animals were slaughtered and fragments of the kidneys were collected for histological analysis. The serum urea level was higher in animals fed a diet based on the Miúda variety (49.38 mg dL-1), and the serum creatinine levels were lower in the last two collections (P = 0.009). The most frequent histopathological findings in the kidneys were calcification, congestion, glomerular atrophy, presence of luminal cellular debris, and nephrosis, regardless of the cactus pear variety. The Miúda cactus pear and OEM cactus pear varieties caused more severe damage to the nephron components, while the varieties IPA F-21 and IPA-Sertânia caused less significant injuries. The use of IPA-Sertânia and IPA F-21 cactus pear varieties is suggested in lamb's diets, due to the lower impact on the renal parenchyma. However, there was no expressive impairment of renal function, and there was no difference between the cactus pear varieties tested in this study on the weight gain of the animals, and they can all be used to feed feedlot sheep.

Cactus cladodes cause intestinal damage, but improve sheep performance.

The objective of this study was to evaluate the effect of three varieties of cactus cladodes resistant to carmine cochineal on the animal performance and histology of the large intestine of sheep. Forty lambs (21.0 ± 2.0 kg body weight) were distributed in a completely randomized design, with four treatments and ten repetitions. The experimental treatments consisted of a control diet and three more diets in which part (750 g/kg) of the elephant grass hay, and all the corn were replaced by Miúda cactus cladodes, IPA-Sertânia cactus cladodes, or Orelha de Elefante Mexicana (O.E.M.) cactus cladodes. On the 60th day after the introduction of the tested diets, blood samples were collected to quantify serum magnesium (Mg2+) levels. After 63 days of experiment, the animals were slaughtered and fragments of the cecum and colon were collected for histopathological analysis. The inclusion of the Miúda and O.E.M. cactus cladodes in the diet caused inflammatory lesions in the cecum (100% of the animals) and in the colon (71.43% of the animals) of the sheep. The inflammation in the cecum caused by Miúda and O.E.M. cactus cladodes was considered accentuated (P = 0.009). Less voluntary water intake was observed for animals submitted to diets with cactus cladodes (P < 0.001), as well as higher water content in the feces (P < 0.001). The cactus cladodes, especially the Miúda and O.E.M. varieties, cause lesions in the tissue morphology of the cecum and colon of sheep, but improve productive performance.

Diethylcarbamazine attenuates the development of carrageenan-induced lung injury in mice.

Diethylcarbamazine (DEC) is an antifilarial drug with potent anti-inflammatory properties as a result of its interference with the metabolism of arachidonic acid. The aim of the present study was to evaluate the anti-inflammatory activity of DEC in a mouse model of acute inflammation (carrageenan-induced pleurisy). The injection of carrageenan into the pleural cavity induced the accumulation of fluid containing a large number of polymorphonuclear cells (PMNs) as well as infiltration of PMNs in lung tissues and increased production of nitrite and tumor necrosis factor-α and increased expression of interleukin-1ß, cyclooxygenase (COX-2), and inducible nitric oxide synthase. Carrageenan also induced the expression of nuclear factor-κB. The oral administration of DEC (50 mg/Kg) three days prior to the carrageenan challenge led to a significant reduction in all inflammation markers. The present findings demonstrate that DEC is a potential drug for the treatment of acute lung inflammation.

Extremely low-frequency magnetic fields can impair spermatogenesis recovery after reversible testicular damage induced by heat.

Male infertility is often related to reproductive age couples experiencing fertility-related issues. Men may have fertility problems associated with reversible testicular damage. Considering that men have been increasingly exposed to extremely low-frequency magnetic fields generated by the production, distribution and use of electricity, this study analyzed whether 60 Hz and 1 mT magnetic field exposure may impair spermatogenesis recovery after reversible testicular damage induced by heat shock using rats as an experimental model. Adult male rats were subjected to a single testicular heat shock (HS, 43 °C for 12 min) and then exposed to the magnetic field for 15, 30 and 60 d after HS. Magnetic field exposure during the spermatogenesis recovery induced changes in testis components volume, cell ultrastructure and histomorphometrical parameters. Control animals had a reestablished and active spermatogenesis at 60 d after heat shock, while animals exposed to magnetic field still showed extensive testicular degeneration. Magnetic field exposure did not change the plasma testosterone. In conclusion, extremely low-frequency magnetic field may be harmful to fertility recovery in males affected by reversible testicular damage.

Bioconjugate based on cisplatin and bacterial exopolysaccharide with reduced side effects: A novel proposal for cancer treatment.

BACKGROUND: In the search for alternatives that attenuate the toxicity associated to oncologic treatment with cisplatin (CDDP) and considering the potential health-beneficial properties of exopolysaccharides (EPS) produced by lactic acid bacteria, it was aimed on this study to evaluate the cytotoxic, toxicologic and antitumoral efficacy of a bioconjugate based on CDDP and EPS, on the experimental tumor of sarcoma 180. METHODS: After the synthesis of the cis-[Pt(NH3)2(Cl)2] complex and of the conjugate containing Lactobacillus fermentum exopolysaccharide was tested both in vitro and in vivo for evaluating the acute toxicity. RESULTS: The antitumoral study was performed using mice transplanted with sarcoma 180. The bioconjugate showed low to medium cytotoxicity for the cell lines tested, as well moderated acute toxicity. After determining the LD50, the following experimental groups were established for the antitumor assay: Control (NaCl 0,9%), CDDP (1 mg/kg), EPS and bioconjugate composition (200 mg/kg). The bioconjugate promoted a 38% regression in tumor mass when compared to the control, and a regression of 41% when compared to CDDP. Liver histopathological analysis revealed discrete alterations in animals treated with (CDDP + EPS) when compared to control. The bioconjugate also minimized changes in the renal parenchyma resulting from the tumor. CONCLUSION: Our results indicate that when CDDP is associated with EPS, this composition was more biocompatible, showing itself as a potent chemotherapeutic agent and lower tissue toxicity.

Endocrine and testicular changes induced by olanzapine in adult Wistar rats.

Olanzapine is an atypical antipsychotic drug that has been increasingly used in acute treatment of, and therapeutic support for, schizophrenia, bipolar disorder and other psychoses. Considering that olanzapine acts on the dopaminergic receptor and this receptor is detected in germ cells, the present study aims to investigate the effects of treatment with different doses of olanzapine on spermatogenesis, plasma testosterone and weight of androgen-dependent organs in rats. Results showed reduced plasma testosterone levels, and reduced testis, epididymis and prostate weights. Histopathologic and histomorphometric analysis of spermatogenesis indicated testicular degeneration. Furthermore, germ cell desquamation, syncytial multinucleated cells, Sertoli cell vacuolization and presence of necrotic and apoptotic germ cells wwew observed. Olanzapine treatment in rats promoted endocrinological changes and lesions in the testis, leading to a disturbance in spermatogenesis.

Enhancement of Scaffold In Vivo Biodegradability for Bone Regeneration Using P28 Peptide Formulations.

The field of bone tissue engineering has shown a great variety of bone graft substitute materials under development to date, with the aim to reconstruct new bone tissue while maintaining characteristics close to the native bone. Currently, insufficient scaffold degradation remains the critical limitation for the success of tailoring the bone formation turnover rate. This study examines novel scaffold formulations to improve the degradation rate in vivo, utilising chitosan (CS), hydroxyapatite (HAp) and fluorapatite (FAp) at different ratios. Previously, the P28 peptide was reported to present similar, if not better performance in new bone production to its native protein, bone morphogenetic protein-2 (BMP-2), in promoting osteogenesis in vivo. Therefore, various P28 concentrations were incorporated into the CS/HAp/FAp scaffolds for implantation in vivo. H&E staining shows minimal scaffold traces in most of the defects induced after eight weeks, showing the enhanced biodegradability of the scaffolds in vivo. The HE stain highlighted the thickened periosteum indicating a new bone formation in the scaffolds, where CS/HAp/FAp/P28 75 µg and CS/HAp/FAp/P28 150 µg showed the cortical and trabecular thickening. CS/HAp/FAp 1:1 P28 150 µg scaffolds showed a higher intensity of calcein green label with the absence of xylenol orange label, which indicates that mineralisation and remodelling was not ongoing four days prior to sacrifice. Conversely, double labelling was observed in the CS/HAp/FAp 1:1 P28 25 µg and CS/HAp/FAp/P28 75 µg, which indicates continued mineralisation at days ten and four prior to sacrifice. Based on the HE and fluorochrome label, CS/HAp/FAp 1:1 with P28 peptides presented a consistent positive osteoinduction following the implantation in the femoral condyle defects. These results show the ability of this tailored formulation to improve the scaffold degradation for bone regeneration and present a cost-effective alternative to BMP-2.

Role of synthetical amynoquinone ethyl 2-(1,4-dioxo-1,4-dihydronaphthalen-2-ylamino) acetate in inhibition of Ehrlich's tumor.

Quinones are naturally or synthetically occurring secondary metabolites that have various bio-dynamics, highlighting their antitumor potential. This has been explored through their selective cytotoxicity, and studies in medicinal chemistry about the relation between biological activity versus chemical structure may lead to the solution of the toxicity problems associated with quinones. In this context, the antitumor effect of a synthetic naphthoquinone, named Ethyl 2-(1,4-Dioxo-1,4-Dihydronaphthalen-2-Ylamino) Acetate, was tested using mice transplanted with Ehrlich ascitic tumor as an experimental model. The acute toxicity test was performed using 30 mice that received the aminoquinone at doses of 100, 200, 300, and 600 mg/kg. After evaluation of the clinical findings in the spontaneous activity tests, the LD50 calculation for the test substance showed low levels of toxicity at doses lower than 244.11 ± 23.29 mg/kg. Thus, three experimental groups were established, where animals transplanted with tumor cells received NaCl vehicle solution (control, n = 6), and the others were treated with 71.7 mg/kg of Methotrexate (n = 6) or 20 mg/kg of Aminoquinone (n = 6). All administrations were intraperitoneal, in a single dose. Three days after the implantation of the tumor cells the animals were weighed daily and evaluated for tumor biometry and development. The treatments occurred five days after the implantation of the tumor cells and were extended for 7 more days. At the end of the 12-day experimental period, all animals were euthanized for biochemical and histopathological analyses of the tumors and vital organs. The spontaneous activity test showed that the amount of responses associated with the nervous system tends to increase with the increase in dosage, highlighting the excitatory effect on the central nervous system in almost all dosages employed, followed by depressant activities on this system. There was a significant tumor reduction, both in animals treated with methotrexate (71.7 %) and in those treated with aminoquinone (91.6 %) in the control group. There was no significant difference in tumor volume between the animals treated with aminoquinone or methotrexate. The histopathological analysis revealed that in both treatments there were fewer mitoses in the tumor mass compared to the control group. However, there was apparent toxicity to the liver, heart, and left kidney in the treatment with methotrexate compared to aminoquinone. The significant capacity for tumor reduction presented by aminoquinone allows pointing it as a promising alternative for the development of a more efficient drug to control tumor development, being necessary for the development of new studies to deepen the knowledge about its mechanisms of action.

Biological activity of 1,2,3-triazole-2-amino-1,4-naphthoquinone derivatives and their evaluation as therapeutic strategy for malaria control.

Malaria can be caused by several Plasmodium species and the development of an effective vaccine is challenging. Currently, the most effective tool to control the disease is the administration of specific chemotherapy; however, resistance to the frontline antimalarials is one of the major problems in malaria control and thus the development of new drugs becomes urgent. The study presented here sought to evaluate the antimalarial activities of compounds derived from 2-amino-1,4-naphthoquinones containing 1,2,3-triazole using in vivo and in vitro models. 1H-1,2,3-Triazole 2-amino-1,4-naphthoquinone derivatives were synthesized and evaluated for antimalarial activity in vitro, using P. falciparum W2 chloroquine (CQ) resistant strain and in vivo using the murine-P. berghei ANKA strain. Acute toxicity was determined as established by the OECD (2001). Cytotoxicity was evaluated against HepG2 and Vero mammalian cell lines. Transmission electron microscopy of the Plasmodium falciparum trophozoite (early and late stages) was used to evaluate the action of compounds derived at ultra-structural level. The compounds displayed low cytotoxicity CC50 > 100 µM, neither did they cause hemolysis at the tested doses and nor the signs of toxicity in the in vivo acute toxicity test. Among the five compounds tested, one showed IC50 values in submicromolar range of 0.8 µM. Compounds 7, 8 and 11 showed IC50 values < 5 µM, and selectivity index (SI) ranging from 6.8 to 343 for HepG2, and from 13.7 to 494.8 for Vero cells. Compounds 8 and 11 were partially active against P. berghei induced parasitemia in vivo. Analysis of the ultrastructural changes associated with the treatment of these two compounds, showed trophozoites with completely degraded cytoplasm, loss of membrane integrity, organelles in the decomposition stage and possible food vacuole deterioration. Our results indicated that compounds 8 and 11 may be considered hit molecules for antimalarial drug discovery platform and deserve further optimization studies.

Fractal methods applied to the seminiferous lumen images can quantify testicular changes induced by heat stress.

Male infertility affects many couples around the world and can be related to environmental factors such as exposure to high temperatures. Even so, automated methods evaluating the seminiferous tubules to detect testicular damage are still scarce. In search of new approaches to automation in the microscopic analysis of the testis; the present study used the fractal dimension, lacunarity, multifractality and quantitative morphometry to quantify changes in microphotographs of the seminiferous lumen in testicles reversibly damaged by heat stress (43 °C, 12 min). The parameters fractal dimension, lacunarity, multifractality (Dq and α), perimeter, feret and circularity were able to detect changes in the seminiferous lumen at 7, 15 and 30 days after the testicular damage. These methods also detected the recovery of spermatogenesis at 60 days after heat stress. Area, f(α), centroid X and Y, roundness, rectangle height and width were unable to detect changes caused by heat stress. In conclusion, computer assisted methods applied to the seminiferous lumen images can be a useful new viewpoint to analyze microscopic changes in the testicles, a fast low-cost tool to assist in the automated quantification of testicular damage.

Neutering is not associated with early-onset urethral obstruction in cats.

OBJECTIVES: The purpose of this study was to evaluate the correlation between clinical aspects and urethral lesions with reproductive status and age at neutering in obstructed male cats. METHODS: All cats with compatible signs of urethral obstruction (UO) treated at the Veterinary Hospital of the Federal Rural University of Pernambuco from 2019 to 2021 were divided into three groups according to their reproductive status: intact; prepubertal neutered; and post-pubertal neutered. Cats with compatible signs of UO were selected for further analysis. Age, clinical signs, age at neutering and age of the first obstructive event were documented. Cats with recurrent obstructive urinary signs or urethral trauma that made catheterization impossible were referred for perineal urethrostomy. The morphology of the excised penises was assessed by histopathological analysis. RESULTS: Of 84 cats with signs of UO included in this study, 28.6% were classified as intact, 28.6% as prepubertal neutered and 42.8% as post-pubertal neutered. Intact cats had a significantly earlier onset of UO compared with prepubertal and post-pubertal neutered cats, as seen by the age at obstruction (3.6 vs 5.7 and 5.5 years, respectively). Similar clinical signs and histopathological lesions were observed in all groups. The main clinical signs observed were stranguria, hematuria and pollakiuria. All cats had some degree of injury in the penile urethra. The most common lesions were hemorrhage, fibrosis and congestion. CONCLUSIONS AND RELEVANCE: It appears that intact cats had an earlier onset of UO than neutered cats, regardless of age at neutering. Urethral histopathological lesions and clinical signs were similar in both groups. Pediatric neutering represents a useful tool in the control of abandoned and stray animals and the consequent dissemination of zoonoses, thus having a positive impact on public health.

Testicular development evaluation in rats exposed to 60 Hz and 1 mT electromagnetic field.

Society has been increasingly exposed to low-frequency electromagnetic fields (EMF), mainly from electricity distribution networks and electro-electronic devices. Aiming to clarify the extension of possible interactions between EMF and testicular development, this study evaluated the effects of exposure to 60 Hz and 1 mT EMF in the maturation of testicular components. Wistar rats were exposed to EMF three times per day for 30 min, between the 13th day of gestation and the 21st postnatal day. Results showed a decrease in the following parameters: tubular diameter and seminiferous tubules area; seminiferous epithelium height; total volume of seminiferous tubule; tubular lumen; seminiferous epithelium; and Leydig cells. On the other hand, an increase was observed in connective tissue cells and blood vessels volume. Plasma testosterone, Sertoli cells population, tubular length and gonadosomatic index did not change when exposed to EMF. Histomorphometric analysis showed that exposure to EMF can promote a delay in testicular development.

Histological evaluation of bone repair using ß-tricalcium phosphate.

OBJECTIVES: The aim of the present study was to evaluate bone repair in defects induced in the cranium of Wistar rats using ß-tricalcium phosphate. STUDY DESIGN: In this research, we used 30 rats, randomly distributed in three groups of 10 animals (G1, G2 and G3), corresponding respectively to time of histological evaluation (7, 15 and 30 days). This was a paired study, a defect being induced in the parietal bone on either side of the median sagittal suture of the animals, being the left-hand side the experimental subgroup (filled by biomaterial) and the right control. The histological evaluation was performed by means of light microscopy. The collected data were submitted to the Fisher Exact test for comparison between the groups and to the McNemar test for comparison between the subgroups (P > 5%). RESULTS: The results showed no statistically significant differences between the groups and bone regeneration was similar at the different times of evaluation. CONCLUSIONS: Therefore, we concluded that ß-tricalcium phosphate has not contributed significantly to repair process of defects induced in the cranium of Wistar rats.

Perspectives for the use of latex peptidases from Calotropis procera for control of inflammation derived from Salmonella infections.

BACKGROUND: Anti-inflammatory properties have been attributed to latex proteins of the medicinal plant Calotropis procera. PURPOSE: A mixture of cysteine peptidases (LPp2) from C. procera latex was investigated for control of inflammatory mediators and inflammation in a mouse model of Salmonella infection. METHODS: LPp2 peptidase activity was confirmed by the BANA assay. Cytotoxicity assays were conducted with immortalized macrophages. Peritoneal macrophages (pMØ) from Swiss mice were stimulated with lipopolysaccharide (LPS) in 96-well plates and then cultured with nontoxic concentrations of LPp2. Swiss mice intravenously received LPp2 (10 mg/kg) and then were challenged intraperitoneally with virulent Salmonella enterica Ser. Typhimurium. RESULTS: LPp2 was not toxic at dosages lower than 62.2 µg/mL. LPp2 treatments of pMØ stimulated with LPS impaired mRNA expression of pro-inflammatory cytokines IL-1ß, TNF-α, IL-6 and IL-10. LPp2 increased the intracellular bacterial killing in infected pMØ. Mice given LPp2 had a lower number of leukocytes in the peritoneal cavity in comparison to control groups 6 h after infection. The bacterial burden and histological damage were widespread in target organs of mice receiving LPp2. CONCLUSION: We conclude that LPp2 contains peptidases with strong anti-inflammatory properties, which may render mice more susceptible to early disseminated infection caused by Salmonella.

Preclinical Evidence of Intra-Articular Autologous Cartilage Micrograft for Osteochondral Repair: Evaluation in a Rat Model.

OBJECTIVE: The search for an effective and long-lasting strategy to treat osteochondral defects (OCD) is a great challenge. Regenerative medicine launched a new era of research in orthopaedics for restoring normal tissue functions. The aim of this study was to test the healing potential of Rigenera micrografting technology in a rat model of OCD by investigating 2 cartilage donor sites. METHODS: Full-thickness OCD was bilaterally created in the knee joints of rats. Animals were randomly divided into 2 groups based on the anatomical site used for micrograft collection: articular (TO) and xiphoid (XA). Micrograft was injected into the knee via an intra-articular approach. The contralateral joint served as the control. Euthanasia was performed 2 months after the set-up of OCD. Histological evaluations foresaw hematoxylin/eosin and safranin-O/fast green staining, the modified O'Driscoll score, and collagen 1A1 and 2A1 immunostaining. Kruskal-Wallis and the post hoc Dunn test were performed to evaluate differences among groups. RESULTS: Histological results showed defect filling in both autologous micrografts. The TO group displayed tissue repair with more hyaline-like characteristics than its control (P < 0.01). A fibrocartilaginous aspect was instead noticed in the XA group. Immunohistochemical assessments on type 2A1 and type 1 collagens confirmed the best histological results in the TO group. CONCLUSIONS: TO and XA groups contributed to a different extent to fill the OCD lesions. TO group provided the best histological and immunohistochemical results; therefore, it could be a promising method to treat OCD after the validation in a larger animal model.

Protective effect of melatonin against herbicides-induced hepatotoxicity in rats.

Exposure to the herbicides Paraquat and Roundup® may cause cell lesions due to an increase in oxidative stress levels in different biological systems, even in the liver. The aim of this study was to analyze the effect of melatonin on liver of rats exposed to herbicides. A total of 35 rats were randomly divided into seven equal-sized groups: control, Paraquat, Roundup®, Paraquat + Roundup®, Paraquat + melatonin, Roundup® + melatonin, and Paraquat + Roundup® + melatonin. Samples of blood and hepatic tissue were collected at the end of the seventh day of exposure and treatment with melatonin. Body weight, hematological parameters, and histopathological, biochemical analyses and determination of oxidative stress levels in liver were evaluated. Body weight was compromised (P < 0.01). Alterations of hematologic parameters were significant when compared to control (P < 0.001). Biochemically, serum levels of albumin decreased (P < 0.001), but serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase increased (P < 0.001). Histopathology revealed necrotic hepatocytes, portal and central-lobular inflammatory infiltrate, congestion of capillaries. Serum levels of thiobarbituric acid reactive substances were found to be significantly elevated (P < 0.05; P < 0.001), and serum level of reduced glutathione was significantly lower (P < 0.05; P < 0.001). The groups treated concomitantly with melatonin revealed results similar to those of the control. However, melatonin acted as a protective agent for the liver against experimentally induced hepatic toxicity, promoting prevention of body weight, oxidative stress, and normalization of hematological and biochemical parameters.