Efficacy of amiodarone and voriconazole combination therapy in cutaneous leishmaniasis in the mice experimentally infected with Leishmania major.

INTRODUCTION: The aim of the present study was to evaluate in vitro and in vivo efficacy of combination therapy of amiodarone and voriconazole against Leishmania major and investigating immune and wound healing responses of cutaneous leishmaniasis to this combination therapy. METHODS: For in vitro study, replication of L. major promastigotes and intracellular amastigotes were investigated in the presence and absence of amiodarone and voriconazole. Isobologram construction and calculation of the Fractional Inhibitory Concentration (FIC) were performed. After the appearance of ulcers on the base of tails of BALB/c mice, treatment was initiated by a combination of amiodarone at 40 mg/kg plus voriconazole at 30 mg/kg orally and glucantime at 60 mg/kg intraperitoneally for 28 consecutive days. RESULTS: According to the concave isobologram and fractional inhibitory concentration <1, combination of amiodarone plus voriconazole had synergistic effects against L. major promastigotes and intracellular amastigotes. There were less inflammatory cells, more fibroblasts and more collagen deposition in tissue sections in the mice treated with combined drugs compared to the vehicle and untreated mice. Increased glutathione peroxidase activity and decreased malondialdehyde, Interleukin-6, and Tumor necrosis factor-α levels were detected in the combination therapy group in comparison to the vehicle and untreated groups. CONCLUSIONS: It seems a combination of amiodarone plus voriconazole can be a rational and promising therapeutic approach in the treatment of cutaneous leishmaniasis.

Effectiveness of amiodarone in treatment of cutaneous leishmaniasis caused by Leishmania major.

Development of new chemotherapeutic agents is an essential issue in the treatment and control of a disease. This study aimed to evaluate the anti-leishmanial activity of amiodarone, an antiarrhythmic class III drug, against Leishmania major, the most prevalent etiological agent of cutaneous leishmaniasis in the old world. The proliferation of promastigotes and intracellular amastigotes in the absence or presence of amiodarone was estimated, in an in vitro study. For in vivo study, five weeks after infection of BALB/c mice with L. major, when the lesions appeared at the injection site, the mice were divided into four groups (n = 6 each); treatment was conducted for 28 consecutive days with vehicle, amiodarone at 40 mg/kg orally and glucantime at 60 mg/kg intraperitoneally. Therapy with amiodarone reduced the size of lesions compared to the untreated group after 12 days. Amiodarone decreased the parasite load and inflammatory responses, particularly the macrophages containing amastigotes, and enhanced granulation tissue formation in the dermis and subcutaneous area. The Tumor necrosis factor-α and Interleukin-6 levels were significantly lower in the cell culture supernatants of the inguinal lymph node in the amiodarone treated group compared to the vehicle and untreated groups. Amiodarone significantly increased the activity of glutathione peroxidase in comparison to the vehicle and untreated groups but did not affect the plasma levels of superoxide dismutase, malondialdehyde, adiponectin, and ferric reducing ability of plasma. Therefore, the anti- L. major activity and immunomodulatory effects of amiodarone reduced the parasitic load and enhanced wound healing in cutaneous leishmaniasis in BALB/c mice. Amiodarone reduced the lesion surface area, but it did not cure it completely.

Burn wound healing: present concepts, treatment strategies and future directions.

Burns are the most extensive forms of soft tissue injuries occasionally resulting in extensive and deep wounds and death. Burns can lead to severe mental and emotional distress, because of excessive scarring and skin contractures. Treatment of burns has always been a difficult medical problem and many different methods have been used to treat such injuries, locally. Biofilms are a collection of microorganisms that delay wound healing. One of the new methods of prevention and treatment of burn wound infections is application of antimicrobials, which act on biofilms and prevent the wound infection. Biofilm initiates a persistent, low-grade, inflammatory response, impairing both the epithelialisation and granulation tissue formation. Skin grafts have been shown to dramatically reduce deaths from infection. However, grafting has considerable limitations. Such injuries are long-lasting and many patients suffer from chronic pain for a long time. Tissue engineering is a new approach in reducing the limitations of conventional treatments and producing a supply of immunologically tolerant artificial tissue, leading to a permanent solution for damaged tissues; such criteria make it a cost-effective and reliable treatment modality. To overcome the present limitations of burn wound healing, knowledge about the latest findings regarding healing mechanisms is important. Here the authors discuss the most important events regarding burn wound healing and review the latest treatment strategies that have been used for burn wounds from in vitro to clinical levels. Finally, we discuss the role of tissue engineering and regenerative medicine in the future of burn wound healing, modelling and remodelling.

A rare case of cerebral hydatidosis caused by a G1 genotype of Echinococcus granulosus in a cow from Iran.

Hydatidosis is a medically and veterinary important parasitic disease that is endemic in many parts of the world. Unilocular hydatid cysts may develop in almost any part of the body. Up to 70% of hydatid cysts are located in the liver, followed by 25% in the lungs. Cerebral hydatidosis is an uncommon manifestation of the disease, occurring in less than 1/1000 infected hosts, yet diagnosis does pose a problem. We have reported an exceptionally rare case of cerebral hydatidosis in cattle. This is the first report to describe the characteristic pathological features of the cerebral hydatidosis in cattle caused by the G1 genotype of Echinococcus granulosus. Genotypic analysis was performed on a hydatid cyst from a cow originating from southern Iran, based on the sequence analysis of the cox1 mitochondrial gene.

Molecular investigation and cultivation of camelpox virus in Iran.

Camelpox virus (genus Orthopoxvirus, family Poxviridae) is the etiologic agent of camel pox. The clinical manifestations of this virus range from inapparent infection to mild, moderate and, less commonly, severe systemic infection and death. Following an outbreak of camelpox, samples that were collected from camel flocks suspected to have camelpox in Qom Province in central Iran and Khash city, Sistan and Baluchestan Province and South Khorasan Province in eastern Iran were sent to Razi Vaccine and Serum Research Institute in Mashhad. DNA extraction was performed primarily by the phenol-chloroform method, and PCR was carried out using a Bioneer kit. Using the primer pair 5'-AAT-ACA-AGG-AGG-ATC-T-3' and 5'-CTT-AAC-TTT-TTC-TTT-CTC-3', the gene sequence encoding the A-type inclusion protein (ATIP) was amplified. The size of the PCR product, specific for camelpox virus, was 881 bp. The PCR product was purified, and to confirm its sequence, it was sent to the reference laboratory. The sequence was subjected to a BLAST search and then phylogenetically analyzed using CLC software. The results showed that all samples were nearly 100 % identical to each other and to strains CMS and M-96. These isolates also had 99 % and 95 % similarity to the CP-1 strain and isolate FIN/T2000, respectively. In Vero cell culture, inoculation with this virus caused a cytopathic effect (CPE), which appeared 2-5 days post-inoculation. Characteristic CPE showing foci of rounded cells, ballooning, giant-cell formation and syncytia with degenerative changes appeared.

Collagen implants in experimental tendon injury in rabbits: a clinical, ultra-structural and biomechanical investigation.

This study investigated the effects of hybridized micro and nano structured collagen implants on tendon healing in an experimental tendon injury in rabbits. Fifty mature male New Zealand white rabbits were randomly divided into two groups of treated and control. Two cm of the left Achilles tendon were discarded. In the treated group, a 3-dimensional (3D) collagen implant was engineered and implanted in the defect area. No implant was used in the control group. At day 120 after injury, the Achilles tendon of the animals were ultrasonographically (days 0-120 after injury) and radiographically (day 120 after injury) examined, and the animals were euthanized. The tendons were dissected and used for gross pathological, histopathological, ultra-structural and biomechanical investigations. Application of the collagen implant significantly increased the diameter of the newly regenerated tissue in the defect area compared to the control tendons. Treatment also significantly increased the echogenicity and homogeneity of the injured area, the diameter of the collagen fibrils and fibers, maturity of the tenoblasts, number of tenocytes, collagen density, alignment, ultimate and yield load, stiffness, stress and modulus of elasticity. The collagen implants were almost totally absorbed 120 days after surgery. No inflammatory reaction or tissue degeneration or necrosis was evident in the treated tendons compared to the control ones. 3D collagen implants produced a newly regenerated tendinous tissue at the defect area that was morphologically and biomechanically superior to the control group. This collagen implant was biocompatible and biodegradable with high bio-safety in rabbits.

The effects of allogeneic and xenogeneic lyophilized leukocyte-and platelet-rich fibrin on bone healing in rat.

BACKGROUND: Critical size defects are one of the challenges in the treatment of fractures in humans and animals. Blood products such as leukocyte-SAand platelet-rich fibrin (L-PRF) are one of the alternatives to bone autograft to solve this challenge. This study aims to evaluate the effects of allogeneic and xenogeneic lyophilized L-PRF on bone healing in a critical defect of radius bone in rat. METHODS: A defect with a diameter of 5 mm was created in the radius bone of 60 rats in four groups. The defect was left empty in the untreated group, and it was filled with autogenous bone graft, allogeneic, and xenogeneic lyophilized L-PRF, respectively, in the other three groups. Radiographic evaluation was done every two weeks, and histopathological evaluation in the 14th, 28th, and 56th days after surgery. RESULTS: The radiographic scores of allogeneic and xenogeneic lyophilized l-PRF groups were significantly higher than the untreated group in all times (P<0.05). In connection with histopathological Emery's scoring system, the score of allogeneic lyophilized L-PRF was significantly higher than the untreated group (P<0.05) in the 14th and 28th days after surgery. The score of the xenogeneic lyophilized L-PRF group was also higher than the untreated group, but the difference was not significant (P>0.05). The allogeneic and xenogeneic lyophilized L-PRF scores were significantly higher than the untreated group (P < 0.05) on the 56th day. CONCLUSION: The results of the present study showed that the allogeneic and xenogeneic lyophilized L-PRF can improve bone healing in the critical radius bone defect in rat model of study.

A long-term in vivo investigation on the effects of xenogenous based, electrospun, collagen implants on the healing of experimentally-induced large tendon defects.

AIM: This study was designed to investigate the effect of novel 3-dimensional (3-D) collagen implants on the healing of large, experimentally-induced, tendon-defects in rabbits. METHODS: Forty mature male white New Zealand rabbits were divided randomly into treated and control groups. Two cm of the left Achilles tendon was excised and the gap was spanned by Kessler suture. In the treated group, a novel 3-D collagen implant was inserted between the cut ends of the tendon. No implant was used in the control group. During the course of the experiment the bioelectrical characteristics of the healing and normal tendons of both groups were investigated weekly. At 120 days post injury (DPI), the tendons were dissected and inspected for gross pathology, examined by transmission and scanning electron microscopy, and their biomechanical properties, percentage dry matter and hydroxyproline concentration assessed. RESULTS: The collagen implant significantly improved the bioelectrical characteristics, gross appearance and tissue alignment of the healed, treated tendons, compared to the healed, control scars. It also significantly increased fibrillogenesis, diameter and density of the collagen fibrils, dry matter content, hydroxyproline concentration, maximum load, stiffness, stress and modulus of elasticity of the treated tendons, as compared to the control tendons. Treatment also significantly decreased peri-tendinous adhesions, and improved the hierarchical organization of the tendon from the collagen fibril to fibre-bundle level. 3-D xenogeneic-based collagen implants induced newly regenerated tissue that was ultrastructurally and biomechanically superior to tissue that was regenerated by natural unassisted healing. CONCLUSION: This type of bioimplant was biocompatible, biodegradable and appeared suitable for clinical use.

Tissue distribution of infectious pancreatic necrosis virus serotype Sp in naturally infected cultured rainbow trout, Oncorhynchus mykiss (Walbaum): an immunohistochemical and nested-PCR study.

This study investigates the occurrence and distribution pattern of infectious pancreatic necrosis virus (IPNV) within the pancreas, liver, kidney and spleen of naturally infected cultured rainbow trout, Oncorhynchus mykiss (Walbaum), using immunohistochemistry (IHC). A nested PCR was also employed to confirm the presence of the virus in the pooled tissues of the specimens. All the examined tissues except spleen were immunohistochemically positive for IPNV, but staining intensity and distribution pattern varied. The kidney tubules had the most intense and widespread staining by IHC, indicating a specific tissue tropism at least for this particular serotype. The nucleotide sequence had the greatest identity with the Sp serotype confirming the presence of the nucleic acid of IPNV in the pooled tissues. Based on the present findings, it could be concluded that the absence of lesions consistent with infectious pancreatic necrosis (IPN) disease in the H&E-stained sections cannot rule out the presence of the IPNV, and the use of an alternative rapid confirmatory method such as IHC with formalin-fixed, paraffin-embedded tissue sections is helpful for the final diagnosis of IPN in rainbow trout.

Effectiveness of synthetic hydroxyapatite versus Persian Gulf coral in an animal model of long bone defect reconstruction.

BACKGROUND: There is a continuing search for bone substitutes to avoid or minimize the need for autogenous bone grafts. Hydroxyapatite, a crystalline phase of calcium phosphate found naturally in bone minerals, has shown tremendous promise as a graft material. Coral is an osteoconductive material used as a bone graft extender. This study examined the effect of hydroxyapatite and Persian Gulf coral on osteogenesis in vivo using a rabbit model of bone healing. MATERIALS AND METHODS: A critical-size defect of 10 mm elongation was created in the radial diaphysis of 36 rabbits and supplied with either hydroxyapatite or coral or left empty (control group). Radiographs of each forelimb were taken postoperatively on day 1 and then at 2, 4, 6, and 8 weeks postinjury to evaluate bone formation, union, and remodeling of the defect. The operated radiuses were removed on the 56th postoperative day and were grossly and histopathologically evaluated. In addition, biomechanical testing was conducted on the operated and normal forelimbs of half of the animals of each group. RESULTS: In radiological evaluation, bone formation and union were significantly superior in the coral and hydroxyapatite groups in comparison with the control group on the 42nd and 56th day postinjury (P < 0.05). There were no statistical differences between groups in remodeling criteria at the 56th day postinjury (P > 0.05). In histopathological evaluation, the union scores of the rabbits administered hydroxyapatite or coral were statistically superior to those of the animals of the control group on the 56th day postinjury (P < 0.05). In biomechanical evaluation, the control group showed weakness of biomechanical properties in comparison with the coral and hydroxyapatite groups (P < 0.05). CONCLUSIONS: According to this study, significant difference was not observed between hydroxyapatite and natural coral and these two materials were significantly better than the control group at 8 weeks postinjury.

Zoledronate loaded polylactic acid/polycaprolactone/hydroxyapatite scaffold accelerates regeneration and led to enhance structural performance and functional ability of the radial bone defect in rat.

Abstract. Background: One of the most common concerns in the regeneration of massive bone defects necessitating surgery and bone grafts is the application of tissue engineering using drug delivery. Zoledronate is a well-known effective drug for the healing bone fractures in osteoporotic patients. Aims: An attempt was made to design a more efficient bone scaffold with polycaprolactone, polylactic acid, and hydroxyapatite. Methods: The scaffold was fabricated by freeze-drying and indirect 3D printing approaches. X-ray diffraction, Fourier transform infrared spectroscopy, rheometry, scanning electron microscopy, and neutral red tests were performed to characterize the scaffold. qRT-PCR was also done to define the osteoinductivity and angiogenic induction capacity of this scaffold. Forty rats were selected and randomly divided into four groups: the control group, which received no treatment, the autograft group, scaffold group, and Zol-loaded scaffold group (n=10 in each group). The injured area was studied by radiology, biomechanical analysis, histopathology, histomorphometry, immunohistochemistry, and CT scan analyses. Results: The qRT-PCR results demonstrated significantly higher expression levels of OPN, OCN, and CD31 markers in the scaffold group when compared to the control group (P<0.05). Histopathologically, the newly formed bone tissue was significantly detected in the Zol-loaded scaffold and autograft groups in comparison with the non-treated group (P<0.001). The immunohistochemistry (OC marker), biomechanical, and histomorphometric results indicated a significant improvement in the regeneration of the injured area in the groups treated with autologous bone and Zol-loaded scaffold compared to the non-treated group (P<0.05). Conclusion: The Zol-loaded scaffold accelerated bone regeneration, and led to enhanced structural performance and functional ability of the injured radial bone in rats.

Human platelet rich plasma plus Persian Gulf coral effects on experimental bone healing in rabbit model: radiological, histological, macroscopical and biomechanical evaluation.

Coral is an osteoconductive material used as a bone graft extender and human platelet rich plasma has been used as a source of osteoinductive factor. A combination of human platelet rich plasma and coral is expected to create a composite with both osteoconductive and osteoinductive properties. This study examined the effect of a combination of human platelet rich plasma and coral on osteogenesis in vivo using rabbit model of bone healing. A critical size defect of 10 mm elongation was created in the radial diaphysis of 36 rabbit and either supplied with coral-human PRP, or coral alone or left empty (control group). The platelets in the PRP were about 10.1 fold compared to normal blood. Radiographs of each forelimb was taken postoperatively on 1st day and then at the 2nd, 4th, 6th and 8th weeks post injury to evaluate bone formation, union and remodeling of the defect. The operated radiuses were removed on 56th postoperative day and were grossly and histopathologically evaluated. In addition, biomechanical test was conducted on the operated and normal forearms of the rabbits. This study demonstrated that coral-human PRP (hPRP), could promote bone regeneration in critical size defects with a high regenerative capacity. The results of the present study demonstrated that coral-hPRP could be an attractive alternative for reconstruction of the major diaphyseal defects of the long bones in animal models.

Modulation of cutaneous wound healing by silymarin in rats.

OBJECTIVE: To investigate the effect of topical application of silymarin on full-thickness cutaneous wounds in rats. METHOD: A full-thickness cutaneous defect (2×2cm) was induced on the back of 85 male and female Wister rats. The animals were randomly divided into four groups (n=20 in each group), treated with 1ml basal cream (placebo group), low-dose (6mg/ml/rat) and high-dose (12mg/ml/rat) silymarin, and untreated (control). Five rats remained uninjured to serve as comparisons for biomechanical analysis. Wounds were evaluated 10, 20 and 30 days after injury, through histopathologic, biochemical and biomechanical analyses. RESULTS: There was a significant (p < 0.05) increase observed in the amount of glycosaminoglycans and collagen present on days 10, 20 and 30 for both low-dose and high-dose silymarin groups. Low-dose silymarin reduced the number of lymphocytes and enhanced the number of fibrocytes at the earlier stages of wound healing; however, high-dose silymarin reduced both lymphocytes and macrophages, and increased number of fibrocytes at the later stages of wound healing. Silymarin significantly improved alignment of the healing tissue, enhanced maturity of the collagen fibres and fibroblasts (p < 0,05), and increased the ultimate tensile strength and stress of the healing tissue. CONCLUSION: The results suggest that topical application of silymarin improved the morphological, biochemical and biomechanical properties of experimentally-induced wound defects in rats. DECLARATION OF INTEREST: There were no external sources of funding for this study. The authors have no conflicts of interest to declare.

Effects of combined hydroxyapatite and human platelet rich plasma on bone healing in rabbit model: radiological, macroscopical, hidtopathological and biomechanical evaluation.

Hydroxyapatite is an osteoconductive material used as a bone graft extender and exhibits excellent biocompatibility with soft tissues such as skin, muscle and gums, making it an ideal candidate for orthopedic and dental implants or components of implants. Synthetic hydroxyapatite has been widely used in repair of hard tissues, and common uses include bone repair, bone augmentation, as well as coating of implants or acting as fillers in bone or teeth. On the other hand, human platelet rich plasma (hPRP) has been used as a source of osteoinductive factor. A combination of hPRP and hydroxyapatite is expected to create a composite with both osteoconductive and osteoinductive properties. This study examined the effect of a combination of hydroxyapatite and hPRP on osteogenesis in vivo, using rabbit model bone healing. A critical size defect of 10 mm long was created in the radial diaphysis of 36 rabbit and either supplied with hydroxyapatite-human PRP or hydroxyapatite or was left empty (control group). Radiographs of each forelimb were taken postoperatively on 1st day and then at the 2nd, 4th, 6th and 8th weeks post injury to evaluate bone formation, union and remodeling of the defect. The operated radiuses of half of the animals in each group were removed on 56th postoperative day and were grossly and histopathologically evaluated. In addition, biomechanical test was conducted on the operated and normal forearms of the other half of the animals of each group. This study demonstrated that hydroxyapatite-humanPRP, could promote bone regeneration in critical size defects with a high regenerative capacity. The results of the present study demonstrated that hydroxyapatite-hPRP could be an attractive alternative for reconstruction of the major diaphyseal defects of the long bones in animal models.

A long term study on the role of exogenous human recombinant basic fibroblast growth factor on the superficial digital flexor tendon healing in rabbits.

BACKGROUND: This study was designed to investigate the effects of basic fibroblast growth factor on the remodeling phase of the tenotomized superficial digital flexor tendon in rabbits. METHODS: Forty white New Zealand mature male rabbits were divided randomly into two equal groups of treated and control. After tenotomy and surgical repair, using modified Kessler technique and running pattern, the injured legs were casted for 14 days. Human recombinant basic fibroblast growth factor (bFGF) was injected subcutaneously over the lesion on days 3, 7 and 10 post injuries. The control animals received normal saline injection similarly. The weight of the animals, tendon diameter, radiographic and ultrasonographic evaluations was conducted at weekly intervals. The animals were euthanized 84 days post-injury and the tendons were evaluated at macroscopic, histopathologic and ultrastructural level and were also assessed for biomechanical and percentage dry weight parameters. RESULTS: Treatment significantly reduced the diameter and increased the echogenicity and dry weight content of the injured tendons. Treatment also significantly enhanced the maturation of the tenoblasts, fibrillogenesis, the collagen fibrils' diameter, fibrillar density, stiffness, and ultimate and yield strength. CONCLUSIONS: Subcutaneous administration of human recombinant bFGF is effective in restoring the morphological and biomechanical properties of the injured SDFT in rabbits.

Histopathologic and ultrastructural studies on experimental caprine besnoitiosis.

The distribution pattern and associated tissue reactions with progressive changes in Besnoitia caprae cysts were investigated in 6 experimentally infected 16- to 20-month-old male goats. Each goat was subcutaneously inoculated with approximately 13 × 10(8) B caprae bradyzoites. The animals were examined daily for development of clinical besnoitiosis, and skin biopsies from distal parts of the limbs were taken at weekly intervals. At 15, 30, 60, 120, 180, and 365 days postinfection (DPI), 1 goat was euthanized. Samples were collected at autopsy from various organs for histologic and ultrastructural studies. No cysts were seen in tissue sections on 15, 30, and 365 DPI, but large numbers were present at 60, 120, and 180 DPI in the skin of the distal limbs, scrotum, and ears, with fewer in the tongue, palate, sclera, testicles, and spermatic cord. No cysts were seen in the lungs, liver, kidneys, spleen, central nervous system, or lymph nodes. Cyst numbers peaked at 60 DPI, then declined from 120 to 180 DPI. Degenerated cysts were relatively rare at 60 DPI but more numerous at 180 compared with 120. A granulomatous reaction--predominantly characterized by macrophages, lymphocytes, and plasma cells--surrounded each degenerated cyst. All goats showed testicular tubular degeneration with little or no spermatogenic activity. The sizes of cysts and their wall thickness, with the size of bradyzoites and some of their organelles, exhibited progressive chronologic changes.

Cytologic, immunocytologic, histopathologic and immunohistologic diagnosis of the poorly differentiated sertoli-leydig cell tumor.

BACKGROUND: Sertoli-Leydig cell tumors (SLCTs), also known as arrhenoblastomas, are tumors of the sex cord-stromal group of ovary and testis cancers. They comprise <1% of all ovarian tumors. They are divided into 6 categories based on the degree of differentiation and the presence of heterologous elements. However, <15% of these tumors are poorly differentiated. CASE: A 23-year-old unmarried female presented with an 8-month history of irregular menstrual cycle and abdominal pain. There were no clinical features suggesting virilization. The left salpingo-oophorectomy specimen revealed an oval ovarian mass of 11 × 7 × 4 cm in dimension. Grossly, the cut surface of the mass was yellowish white in color and solid in consistency and touch preparation was made. By applying cytology and immunocytochemistry techniques, a preliminary diagnosis suggestive of poorly differentiated SLCT was made. The tumor was confirmed as a poorly differentiated SLCT. CONCLUSION: Cytology and immunocytochemistry by WT-1, melan A, vimentin and calretinin are helpful in the diagnosis of poorly differentiated SLCTs.

Effectiveness of mesenchymal stem cell-seeded onto the 3D polylactic acid/polycaprolactone/hydroxyapatite scaffold on the radius bone defect in rat.

PURPOSE: The importance of regeneration in large bone defects forces the orthopedic surgeons to search for a proper methodology. The present experiment evaluated the capability of polylactic acid/polycaprolactone/hydroxyapatite (PLA/PCL/HA) scaffold loaded with and without mesenchymal stem cells (MSCs) on bone regeneration. METHODS: Fourier transform infrared spectrometry, X-ray diffraction, scanning electron microscopy, and rheology methodologies were used to characterize the scaffold. Forty Wistar rats were randomly divided into the four groups including the untreated defects as the control group and three other groups in which the bone defects were treated with autologous bones (autograft group), the PLA/PCL/HA scaffolds (PLA/PCL/HA group), and the MSCs-seeded scaffolds (MSCs-seeded PLA/PCL/HA group). RESULTS: Based on the qRT-PCR results, significantly higher expression levels of osteocalcin, osteopontin, and CD31 were seen in the cell-seeded scaffold group compared to the control group (P < 0.05). The CT scanning and radiographic images depicted significantly more newly formed bonny tissue in the MSCs-loaded scaffold and autograft groups than the untreated group (P < 0.001). The immunohistochemistry, biomechanical, histopathologic, and histomorphometric evaluations demonstrated significantly improved regeneration in the autograft and MSCs-loaded scaffold groups compared to the non-treated group (P < 0.05). There were significant differences between the scaffold and untreated groups in all in vivo evaluations (P < 0.05). CONCLUSION: The MSCs enhanced bone healing potential of the PLA/PCL/HA scaffold and the MSCs-seeded scaffold was comparable to the autograft as the golden treatment regimen (P > 0.05).

Emerging role of amiodarone and dronedarone, as antiarrhythmic drugs, in treatment of leishmaniasis.

Leishmaniasis is a group of human and animal diseases causing 20,000-40,000 annual deaths and its etiological agents belong to the Leishmania genus. The most current treatment against leishmaniasis is chemotherapy. Pentavalent antimonials such as glucantime and pentostam have been administrated as the first-line drugs in treatment of various forms of leishmaniasis. The second-line drugs such as amphotericin B, liposomal amphotericin B, miltefosine, pentamidine, azole drugs and paromomycin are used in resistant cases to pentavalent antimonials. Because of drawbacks of the first-line and second-line drugs including adverse side effects on different organs, increasing resistance, high cost, need to hospitalization and long-term treatment, it is necessary to find an alternative drug for leishmaniasis treatment. Several investigations have reported the effectiveness of amiodarone, the most commonly used antiarrhythmic drug, against fungi, Trypanosomes and Leishmania spp. in vitro, in vivo and clinical conditions. Moreover, the beneficial effects of dronedarone, amiodarone analogues, against Trypanosoma cruzi and Leishmania mexicana have recently been demonstrated and such treatment regimens resulted in lower side effects. The anti- leishmanial and anti- trypanosomal effectiveness of amiodarone and dronedarone has been attributed to destabilization of intracellular Ca2+ homeostasis, inhibition of sterol biosynthesis and collapse of mitochondrial membrane potential. Because of relative low cost, excellent pharmacokinetic properties, easy accessibility and beneficial effects of amiodarone and dronedarone on leishmaniasis, they are proper candidates to replace the current drugs used in leishmaniasis treatment.