Development, Histological, and Ultrastructural Evaluation of Sheep Hyperimmune Serum Therapy for COVID-19 / Desarrollo, Evaluación Histológica y Ultraestructural de la Terapia con Suero Hiperinmune de Oveja para COVID-19

SUMMARY: In response to the threat posed by new variants of SARS-CoV-2 and the urgent need for effective treatments in the absence of vaccines, the aim of this study was to develop a rapid and cost-effective hyperimmune serum (HS) derived from sheep and assess its efficacy. The utilization of a halal-certified, easily maintained in certain geographic regions, easy-to-handle animal such as sheep could provide a viable alternative to the expensive option of horses. Sheep were immunized with a whole inactivated SARS-CoV- 2 antigen to produce HS, which was evaluated for neutralizing potency using the PRNT50 assay. K18-hACE2 transgenic mice (n=35) were divided into three groups: control, SARS-CoV-2 exposure through inhalation, and SARS-CoV-2 exposed mice treated with HS. HS efficacy was assessed through serum proinflammatory cytokine levels, qRT-PCR analysis, histopathological examination of lungs and hearts, and transmission electron microscopy. Purified HS exhibited significant neutralizing activity (1/24,576). The SARS-CoV-2+HS group showed lower levels of TNF-α, IL-10, and IL-6 (P<0.01) and relatively lower levels of MCP-1 compared to the SARS-CoV-2 group. HS prevented death, reduced viral RNA levels in the lungs and hearts, protected against severe interstitial pneumonia, preserved lung tissue integrity, and prevented myocyte damage, while the SARS-CoV-2 group exhibited viral presence in the lungs. This study successfully developed a sheep-derived HS against the entire SARS-CoV-2 virus, resulting in a significant reduction in infection severity, inflammation, and systemic cytokine production. The findings hold promise for treating severe COVID-19 cases, including emerging viral variants, and immunocompromised patients.

En respuesta a la amenaza que suponen las nuevas variantes del SARS-CoV-2 y la urgente necesidad de tratamientos eficaces en ausencia de vacunas, el objetivo de este estudio fue desarrollar un suero hiperinmune (HS) rápido y rentable derivado de ovejas. y evaluar su eficacia. La utilización de un animal con certificación halal, de fácil mantenimiento en determinadas regiones geográficas y de fácil manejo, como las ovejas, podría proporcionar una alternativa viable a la costosa opción de los caballos. Las ovejas fueron inmunizadas con un antígeno de SARS-CoV-2 completamente inactivado para producir HS, cuya potencia neutralizante se evaluó mediante el ensayo PRNT50. Los ratones transgénicos K18-hACE2 (n = 35) se dividieron en tres grupos: control, exposición al SARS-CoV-2 mediante inhalación y ratones expuestos al SARS-CoV-2 tratados con HS. La eficacia de HS se evaluó mediante niveles de citoquinas proinflamatorias en suero, análisis qRT-PCR, examen histopatológico de pulmones y corazones y microscopía electrónica de transmisión. El HS purificado exhibió una actividad neutralizante significativa (1/24,576). El grupo SARS-CoV-2+HS mostró niveles más bajos de TNF-α, IL-10 e IL-6 (P<0,01) y niveles relativamente más bajos de MCP-1 en comparación con el grupo SARS-CoV-2. HS evitó la muerte, redujo los niveles de ARN viral en los pulmones y el corazón, protegió contra la neumonía intersticial grave, preservó la integridad del tejido pulmonar y evitó el daño de los miocitos, mientras que el grupo SARS-CoV-2 exhibió presencia viral en los pulmones. Este estudio desarrolló con éxito un HS derivado de ovejas contra todo el virus SARS-CoV-2, lo que resultó en una reducción significativa de la gravedad de la infección, la inflamación y la producción sistémica de citocinas. Los hallazgos son prometedores para el tratamiento de casos graves de COVID- 19, incluidas las variantes virales emergentes y los pacientes inmunocomprometidos.

SARS-CoV-2 Causes Brain Damage: Therapeutic Intervention with AZD8797.

Elevated CX3CL1 is associated with severe COVID-19 and neurologic symptoms. We aimed to investigate the potential protective effects of selective CX3CR1 antagonist AZD8797 on SARS-CoV-2-induced neuronal damage, and to identify the underlying mechanisms. K18-hACE2 transgenic mice (n = 37) were randomly divided into control groups and SARS-CoV-2 groups, with and without intraperitoneal administration of vehicle or AZD8797 (2.5 mg/mL/day), following exposure to either a single dose of SARS-CoV-2 inhalation or no exposure. Object recognition and hole board tests were performed to assess memory function. Postinfection 8 days, brain tissues were analyzed for histopathological changes, viral, glial, apoptotic, and other immunohistochemical markers, along with measuring malondialdehyde, glutathione, and myeloperoxidase activities. Serum samples were analyzed for proinflammatory cytokines. The SARS-CoV-2 group showed significant weight loss, neuronal damage, oxidative stress, and impaired object recognition memory, while AZD8797 treatment mitigated some of these effects, especially in weight, apoptosis, glutathione, and MCP-1. Histopathological analyses supported the protective effects of AZD8797 against SARS-CoV-2-induced damage. The CX3CL1-CX3CR1 signaling pathway could offer a promising target for reducing SARS-CoV-2's neurological impact, but additional research is needed to confirm these findings in combination with other therapies and assess the clinical significance.

Aortic ischemia-reperfusion injury and potency of fluoxetine.

Objectives: Due to cross-clamping of the aorta during aortic aneurysm surgeries, ischemia-reperfusion (IR) develops, and it may cause damage to the aorta itself or even to remote organs by oxidative stress or inflammation. Fluoxetine (FLX) which might be used in the preoperative period for its tranquilizing effect also has antioxidant effects in short-term use. The purpose of our study is to examine whether FLX protects aorta tissue, against the damage caused by IR. Materials and Methods: Three groups of Wistar rats were formed randomly. 1) Control group (sham-operated), 2) IR group (60 min ischemia+120 min perfusion), and 3) FLX+IR group (FLX dose was 20 mg/kg for 3 days IP before IR). At the end of each procedure, aorta samples were collected, and oxidant-antioxidant, anti-inflammatory, and anti-apoptotic status of the aorta were evaluated. Histological examinations of the samples were provided. Results: Levels of LOOH, MDA, ROS, TOS, MPO, TNFα, IL-1ß, IL-6, NF-kB, MMP-9, caspase-9, 8-OHdG, NO, and HA were found to be significantly increased in the IR group compared with control (P<0.05) and SOD, GSH, TAS, and IL-10 levels were significantly lower (P<0.05). FLX significantly decreased LOOH, MDA, ROS, TOS, MPO, TNFα, IL-1ß, IL-6, NF-kB, MMP-9, caspase-9, 8-OHdG, NO, and HA levels in the FLX+IR group compared with IR group (P<0.05) and increased IL-10, SOD, GSH, and TAS (P<0.05). FLX administration prevented the deterioration of aortic tissue damage. Conclusion: Our study is the first study that demonstrates FLX-mediated suppression of IR injury in the infrarenal abdominal aorta by antioxidant, anti-inflammatory, and anti-apoptotic properties.

Evidence for residual SARS-CoV-2 in corpus cavernosum of patients who recovered from COVID-19 infection.

BACKGROUND: The COVID-19 is an ongoing health problem with millions of cases and deaths worldwide. Although the virus is transmitted with droplets through the respiratory system, the involvement of different organs has been reported. OBJECTIVES: The pandemic caused urological procedures to be postponed when patient is infected with SARS-CoV-2. However, the reliability of 1 month postpone period and long-term complications of the virus, such as a possible erectile dysfunction (ED) is not clarified. We aimed to compare the corpus cavernosum of patients 1 and 7 months after COVID-19 infection with control patients who had not COVID-19 and search for SARS-CoV-2 in tissues using immunohistochemistry and electron microscopy. MATERIALS AND METHODS: Three groups of subjects underwent penile prosthesis implantation and Nesbit procedure for Peyronie's disease 1 and 7 months after COVID-19 infection and control group without previous COVID-19 infection. We searched for SARS-CoV-2 in penile tissue using RT-PCR, electron microscopy and immunohistochemistry. RESULTS: Electron microscopy and immunohistochemical staining showed SARS CoV-2 virus in the penile corpus cavernosum of patients 1 month after COVID-19 recovery. Immunohistochemical staining intensity correlated with the severity of previous infection. Transmission electron microscopy revealed intracellular virtual particles of about 80 nm with a typical morphology of prominent spikes and electron-dense dots of nucleocapsid in addition to vesicles filled with virus-like particles. Cells showed increased membrane trafficking. The 1 month after COVID-19 group showed an increased number of fibroblasts. The 7 months after COVID-19 group had similar morphology and immunoreactivity as control group. DISCUSSION: This is the first study of late post-COVID examination of penis and the second study of early post-COVID examination of corpus cavernosum. For 1 month post-COVID patients, the aetiology of ED could be the viral infection that is also affecting corpora cavernosa. We hypothesize that viral infection affects the endocytic and exocytic pathways, hence the metabolic activity of cells that can be the reason of altered functions in some post-COVID patients. CONCLUSION: This study is important because it did not detect any virus residue in the tissue samples at the seventh month. In addition, we can say that the penile surgeries should be postponed more than 1 month after the COVID infection according to this study. But, there is a need for new studies with large series and high levels of evidence that can show how long the virus remains in the corpus cavernosum. Patients should be followed in this respect.

A newly developed carrier for the vitrification of prepubertal testicular tissue and its comparison with four different carriers.

RESEARCH QUESTION: The cryopreservation of prepubertal testicular tissue is important for children who are to undergo gonadotoxic treatment. There is ongoing debate around the optimal carrier for an inexpensive and rapid vitrification technique. How efficient would a novel, practical and sterilizable metal brush be when compared with previously used carriers? DESIGN: The testicular tissues of prepubertal rats were vitrified using four different carriers and evaluated by light microscopy and transmission electron microscopy. RESULTS: Nuclei were easily discriminated in the metal brush, aluminium foil and high-security straw groups, but there was decreased discrimination of structures in the metal wire group. Minimal cytoplasmic degeneration, vacuolization and mild reversible degenerative effects were seen in spermatogonial stem cells and Sertoli cells in the metal brush group. Mild to moderate structural changes were found in the aluminium foil group. Severe pyknosis of the nuclei, a high degree of swelling, expansion of the endoplasmic reticulum, and swelling and blurring of the mitochondria were seen in the metal wire and high-security straw groups. The cell viabilities in the metal brush, aluminium foil, metal wire and high-security straw groups were 91.6 ± 3.85%, 83.0 ± 4.06%, 76.0 ± 3.16% and 68.6 ± 4.93%, respectively. CONCLUSIONS: The metal brush is a promising new carrier for prepubertal testis vitrification.

Histopathologic evaluation of saphenous vein grafts in patients with type II diabetes mellitus undergoing coronary artery bypass grafting.

INTRODUCTION: Diabetes Mellitus (DM) has been known to be a risk factor for the development of more severe form of saphenous vein graft disease after coronary artery bypass grafting (CABG). We aimed to evaluate the impact of type II-DM on histopathological features of great saphenous vein grafts of patients undergoing CABG. PATIENTS AND METHODS: Forty consecutive patients undergoing elective CABG were enrolled into the study. Patients were grouped into two; Diabetic group (n = 20); includes patients with preoperative diagnosis of type II-DM and Nondiabetic group (n = 20): those without type II-DM. In all patients, a short segment of the great saphenous vein graft at the level of medial malleolus was taken for light microscopy and transmission electron microscopy (TEM) evaluation. Moreover, immunoexpressions of Caveolin-1, Vascular cell adhesion protein 1 (VCAM-1) and endothelial nitric oxide synthase (eNOS) were studied. RESULTS: There were no differences in the demographics of patients between two groups. The magnitude of intimal fibrosis in diabetic group was slightly higher than in nondiabetics (1.95 ± 0.99 versus 1.3 ± 0.8, P = .04). In TEM, vacuolization in endothelial cells, substance accumulation along with coarse collagen fibers and cytoplasmic degeneration with vacuolization in muscle cells were detected in diabetic group. While there were no differences in Caveolin-1 and VCAM-1 immunostaining, the intensity of positive eNOS immunostaining was significantly higher in endothelium (2.10 ± 0.64 versus 1.55 ± 0.68, P = .01) and tunica media 1.75 ± 0.63 versus 1.2 ± 0.52, P = .007) in nondiabetic group, respectively) compared with diabetic group. CONCLUSION: Type II DM might be a reason for decreased expression of eNOS and increased intimal fibrosis, vacuolization of endothelial and smooth muscle cells in saphenous vein grafts. The clinical implications of these alterations on the graft patency need to be evaluated.

Mass and non-mass breast MRI patterns: a radiologic approach to sick lobe theory.

BACKGROUND: According to sick lobe theory, one or more lobes of the breast are more prone to the development of carcinoma. However, the implications of this theory in breast magnetic resonance imaging (MRI) are unknown. PURPOSE: To evaluate the MRI appearance of mass type (multifocal and multicentric diseases) and non-mass type (non-mass enhancements) sick lobe patterns, together with the histopathology results. MATERIAL AND METHODS: MRI reports of 2015 patients in two tertiary breast imaging centers between June 2012 and June 2018 were retrospectively reviewed for multifocal-multicentric diseases and segmental, linear, and regional enhancements. A total of 113 patients were included. The specimens obtained by thick needle, vacuum, excisional biopsy/lumpectomy or mastectomy after breast MRI scans were pathologically assessed. The pathologic results were categorized as invasive carcinoma, precursor, and benign proliferative lesions according to the 2012 World Health Organization Classification of Tumors. RESULTS: The percentage of underlying benign and precursor invasive lesions was significantly different in patients with mass and non-mass MRI patterns. While the pathology results of mass type patterns were premalignant and malignant in all cases, nearly half of the underlying histologies were benign proliferative subtypes in patients with non-mass type patterns. CONCLUSION: In this study, the mass and non-mass patterns derived from sick lobe theory were related to different risks of malignancy in the pathological examinations.

Can tissue elemental analysis be used to differentiate sarcoidosis and tuberculous lymphadenitis?

INTRODUCTION: Sarcoidosis and tuberculous lymphadenitis are granulomatous inflammatory diseases. Differentiating lymph node involvement in these two diseases can be challenging. This study evaluated whether elemental analysis of tissue samples could facilitate the differentiation of these histopathologically and clinically similar diseases. MATERIALS AND METHODS: A total of 152 tissue samples were included: 57 caseating granulomatous inflammation, 58 non-caseating granulomatous inflammation, and 37 reactive lymph node specimens. The tissue samples were analyzed for calcium, magnesium, iron, copper, zinc, chrome, molybdenum, nickel and selenium with inductively coupled plasma-optical emission spectroscopy (ICP-OES). RESULT: Comparison of element levels in the three groups revealed that caseating granulomatous inflammation had higher calcium content (662.6 ± 4.6 ppm, p< 0.001) and lower iron content (48.7 ± 83 ppm, p< 0.001) compared to non-caseating granulomatous inflammation. Compared to reactive lymph tissue, caseating granulomatous inflammation had higher calcium and lower iron and magnesium content while non-caseating granulomatous inflammation had higher levels of iron and lower magnesium; however, these differences were not statistically significant. In caseating granulomatous inflammation, a calcium cut-off value of 207 ppm yielded 85% specificity and 63% sensitivity. For iron, a cut-off value of 51 ppm had 74% specificity and 58% sensitivity. CONCLUSIONS: High calcium and low iron levels in lymph tissue may be suggestive of caseating granulomatous inflammation and tuberculosis. In cases where differentiating between sarcoidosis and tuberculous lymphadenitis is difficult, performing tissue elemental analysis may provide additional supportive evidence for differential diagnosis.

Milrinone Attenuates Heart and Lung Remote Injury after Abdominal Aortic Cross-Clamping.

BACKGROUND: Phosphodiesterase enzymes play a pivotal role in the pathogenesis of ischemia/reperfusion (IR). We examined the role of milrinone (MIL), a phosphodiesterase 3 inhibitor, on remote injury of the heart and lung after abdominal aortic cross-clamping. DESIGN: Experimental study. METHODS: Twenty-one Wistar rats were divided into 3 groups: (1) control (C, n = 7), underwent laparotomy and exploration of abdominal aorta only; (2) IR (n = 7), normal saline was applied intraperitoneally (i.p) before IR induced by clamping of the abdominal aorta for 1 hr and then allowing reperfusion for 1 hr; and (3) MIL + IR (n = 7), MIL was given (0.5 mg/kg, i.p) before IR. After sacrification, the lungs and hearts were taken out for analyses and the tissue malondialdehyde (MDA) and glutathione (GSH) were studied. All tissues were examined under light microscopy and transmission electron microscopy (TEM). Expressions of caveolin (Cav)-1 in the lung and Cav-1 and Cav-3 in the heart were examined immunohistochemically. RESULTS: The MIL + IR group had significantly a lower magnitude of oxidative stress than the IR group both in the lung and heart (lung: P = 0.03 for MDA and 0.001 for GSH and heart: P = 0.002 for MDA and 0.000 for GSH). In light microscopy, the MIL + IR group had statistically a lower total injury score than the IR group for both the lung and heart tissue (P = 0.03 and P = 0.04, respectively). In TEM, regression of mitochondrial degeneration and lamellar bodies in type II pneumocytes in the lungs and obvious improvements in disruption at the intercalated discs and mitochondrial degeneration in the hearts in the MIL + IR group were detected compared with the IR group. The expression of both Cav-1 and Cav-3 in the MIL + IR group was improved compared with the IR group (P = 0.03 for both). CONCLUSIONS: MIL attenuates remote injury of heart and lung in lower body IR by inhibiting oxidative stress. Moreover, Cav-1 and Cav-3 might have a potential role in MIL-induced cardioprotection.

A New Method to Harvest the Sural Nerve Graft.

OBJECTIVE: In this study, we developed a novel technique to harvest the sural nerve using the mini incisions and the carpal tunnel dilators. MATERIALS AND METHODS: The technique was applied to the 29 sides on 27 patients (24 men and 3 women). The mean age was 27.1 years (range 9-51). The diagnoses were soft tissue traumas in 23 cases, fracture in 2 cases, and previous complicated operation in 2 cases. The harmful effects of harvest procedure on the sural nerve graft were assessed double-blind histopathologically and compared with control group. RESULTS: All the nerve grafts were successfully harvested with no macroscopic damage to the sural nerve graft. There was no statistically significant difference between the histopathologic scores of the distal and proximal nerve segments (p>0.05). The average follow-up time was 17 months (range 8-46). In the postoperative period, no complication such as massive bleeding/hematoma, wound infection, skin necrosis, painful neuroma formation, or prolonged calf tenderness was observed. In all cases, there were inconspicuous scars. CONCLUSION: The method seems safe and has no damage on the nerve graft histopathologically. We believe that this technique may be used in future.

Bacterial cellulose tubes as a nerve conduit for repairing complete facial nerve transection in a rat model.

PURPOSE: Functionality of the facial nerve is cosmetically important. While many techniques have been investigated, early and effective treatment for traumatic facial nerve paralysis remains challenging. Here, we aim to examine bacterial cellulose (BC) as a new tubularization material for improving facial nerve regeneration. METHODS: Our study was performed on 40 female Sprague Dawley rats. Rats were randomly divided into four groups, with 10 rats per group. In all rats, the main trunk of the facial nerve was completely cut 8 mm before the branching point. For repairing the facial nerve, in group 1, the nerve was left to recover spontaneously (control group); in group 2, it was repaired by primary suturing (8.0 Ethilon sutures, Ethicon); in group 3, BC tubes alone were used to aid nerve repair; and in group 4, both BC tubes and primary sutures (8.0 Ethilon sutures) were used. After 10 weeks, the facial nerve regeneration was evaluated by the whisker movement test and electrophysiologically (nerve stimulation threshold and compound muscle action potential). Nerve regeneration was assessed by calculating the number of myelinated nerve fibers, and by microscopically evaluating the amount of regeneration and fibrosis. RESULTS: No significant difference was observed among the groups in terms of whisker movement and electrophysiological parameters (P > 0.05). We found that the numbers of regenerating myelinated fibers were significantly increased (P < 0.05) when BC tubes were used as a nerve conduit. CONCLUSIONS: BC can be easily shaped into a hollow tube that guides nerve axons, resulting in better nerve regeneration after transection.

Effect of Vasa Vasorum on Basilar Artery Vasospasm Following Subarachnoid Hemorrhage.

BACKGROUND: A well-documented association exists between the vasa vasorum and vasopathologies, including atherosclerosis. However, information on the role of the vasa vasorum during vascular degenerative changes of vasospasm after subarachnoid hemorrhage (SAH) is insufficient. METHODS: In this study, 34 rabbits were divided into 3 groups: basal group (N = 8), sham group (N = 8), and SAH group (N = 18). Experimental SAH was formed using a double-injection model. During follow-up, the neurologic status of the rabbits was observed. All rabbits were euthanized after 2 weeks, and the vasopathologic degeneration was categorized as normal, mild, moderate, and severe according to the changes in the basilar arteries. The numbers, locations, and spasms of the vasa vasorum and their relation to the vasodegenerative changes of the basilar artery were investigated. RESULTS: The basilar arteries were graded as normal in the basal and sham groups. In the SAH group, 6 rabbits had mild, 7 had moderate, and 5 had severe degeneration. Neurologic deficits were prominent in the SAH group, and deficit grades correlated with vascular degeneration. The number of the vasa vasorum were significantly higher in the SAH group, and an enhanced formation of the vasa vasorum was noted in which severe degenerative changes were present. Moreover, the vasospasm index of the vasa vasorum, which increased with the aggravation of vascular degenerative changes, was significantly higher in the SAH group. CONCLUSIONS: The vasa vasorum and their vasospasm play a crucial role in the pathogenesis of basilar artery degeneration in the vasospasm following SAH.

Cervical Thymic Cyst Around Hypoglossal Nerve.

Cervical thymic cyst is rare lesions leading to cervical mass. As it is a rare entity, it might be confused with other congenital neck masses or neoplastic lesions. Preoperative diagnosis is almost impossible. In the present study, a patient who was operated with prediagnosis of branchial cyst and diagnosed with thymic cyst according to the histopathologic examination was presented. A 16-month-old girl was admitted to our clinic with the complaint of growing right neck mass that was realized about 4 months ago. Magnetic resonance imaging (MRI) of the neck demonstrated a rim-enhanced hypointense cystic lesion in the posterior aspect of the submandibular gland, without tracheal right lateral and mid plane on MRI, curving common carotid artery to the medial. Patients underwent surgery under general anesthesia in company with existing findings. Hypoglossal nerve was surrounded by the mass, and the mass was totally resected. The final pathology result was reported as thymic cyst. Cervical thymic masses might be unnoticed in the differential diagnosis of the cervical mass as they are rarely seen entities. Histopathologic examination of the thymus tissue was performed for diagnosis. Surgical excision is the ideal treatment approach and no postoperative recurrence has been reported.

A novel method for flap delay vacuum assisted flap delay: an experimental study in rabbits.

Flaps are the workhorse of plastic surgery practice. The delay procedures have been defined to prevent flap necrosis. The golden standard method of delay is a surgical delay. On the other hand, a major drawback of surgical delay is two sessions of surgery. Efforts have been made to omit one session and increase the patient safety and decrease the costs. The writer's aim was to evaluate the effects of topical negative pressure, applied prior to flap elevation, on flap survival, perfusion and compare the results with the surgical delay. In a rabbit random flap model, prior to elevation, the writers used a topical negative pressure system on the lateral thoracic region of, for induction of delay and compared the results with surgical delay and the control group. The total and necrotic flap areas, necrosis ratio, histomorphometric vascular density, immunohistochemical evaluation of neovascularization (CD31/CD34), Laser Doppler images and computerized tomography contrast uptake were used to compare the groups. In all of the parameters, the vacuum assisted flap delay was equivalent to surgical delay. Both were superior to non-delayed flaps. Control group had 65.56 ± 18.02% flap necrosis rate, while Surgical Delay group had 37.31 ± 30.74% and Vacuum Assisted Flap Delay group had 19.58 ± 27.35%. Vacuum Assisted Flap Delay did not require an extra operation for the delay procedure. The mechanism of action in the vacuum-assisted flap delay is unclear. The clinical significance should be studied further. However, vacuum assisted flap delay seems to be a promising method in the clinical setting.

Brachial Artery Vasospasm Caused by Cervical Dorsal Root Ganglion Degeneration After Subarachnoid Hemorrhage: An Experimental Study.

PURPOSE: Subarachnoid hemorrhage (SAH) may lead to vasospasm in various vessels. The cervical nerves have a vasodilatory effect on the upper extremity arteries. The aim of this study was to investigate if there is a relationship between C6 dorsal root ganglion (DRG) degeneration and brachial artery (BA) vasospasm after spinal SAH. METHODS: This experimental study was conducted on 23 rabbits. The animals were divided into 3 groups: control (n = 5), SHAM (n = 5), and study group (n = 13). One cubic centimeter (cc) of serum saline was injected into the cisterna magna of animals of the SHAM group; the same procedure was performed by 1 cc of homologous blood in the study group. Degenerated neuron densities (DNDs) of DRGs (n/mm3) at C6 levels and BA vasospasm indexes (VSI; wall surface/lumen surface) of all animals were determined and results were analyzed statistically. RESULTS: Mean VSI values of BAs and DNDs of C6DRGs of the control, SHAM, and study groups were estimated as 10 ± 3/1.12 ± 0.11 n/mm3, 34 ± 9/1.27 ± 0.24 n/mm3, and 1031 ± 145/2.93 ± 0.78 n/mm3, respectively. Mean DNDs and VSI values were statistically significantly different between the control and study groups (P < 0.0001). CONCLUSIONS: C6DRG degeneration may be considered as an important factor in the etiopathogenesis of severe BA vasospasm after SAH.

Effect of ethyl acetate extract of usnea longissima on esophagogastric adenocarcinoma in rats1.

PURPOSE: To investigate the effects of the EtOAc extract of U. longissima which is uninvestigated previously on esophagogastric cancer induced in rats with N-methyl-N-nitro-N-nitrosoguanidin (MNNG). METHODS: The anticancer activity of EtOAc extract of U. longissima was examined in the esophagogastric adenocarcinoma models induced in rats with MNNG. EtOAc extract of U. longissima, 50 and 100 mg/kg oral doses were administered once daily for six months. MNNG induced differentiated and undifferentiated type adenocarcinomas in the esophageal and gastric tissues of rats. RESULTS: EtOAc extract of U. longissima obtained from U. longissima prevented gastric and esophageal cancerogenesis induced in rats with MNNG. EtOAc extract of U. longissima did not have a lethal effect at doses of 500, 1000 and 2000 mg/kg. The prominent anticarcinogenic activity of EtOAc extract of U. longissima 50 and 100 mg/kg suggests that it is not toxic and it is selective to the cancer tissue. CONCLUSION: This information may shed light on clinical implementation of EtOAc extract of U. longissima in future.

Therapeutic effects of caffeic acid phenethyl ester on alveolar bone loss in rats with endotoxin-induced periodontitis.

BACKGROUND/PURPOSE: Caffeic acid phenethyl ester (CAPE) is an antioxidant which is decreases the bone resorption and enhances the bone healing. The aim of this study was to investigate the effects of administering systemic CAPE on alveolar bone loss in rats with experimental periodontitis. MATERIALS AND METHODS: Thirty male Sprague Dawley rats were divided into three groups: control, endotoxin-induced periodontitis (EP), and EP treated with CAPE (EP-CAPE). Endotoxin was injected into the gingiva of test rats on days 1, 3, and 5, whereas saline was injected into the control rats. The EP-CAPE group received 10 mmol/kg/day CAPE intraperitoneally for 28 consecutive days. Saline was given in the control and EP groups in the same manner. At the end of the study, intracardiac blood samples were obtained, and the rats were sacrificed. Alveolar bone loss was analyzed with histometric measurements. The oxidative stress index (OSI) was used to evaluate the oxidative stress. The receptor activator of the nuclear factor kappa B ligand (RANKL) level was analyzed stereologically. RESULTS: CAPE administration significantly decreased the serum OSI and interleukin-1ß levels. Alveolar bone loss was statistically higher in the EP group compared with the EP-CAPE group (P < 0.05). Immunohistochemical analyses of the RANKL were significantly lower in the EP-CAPE group than in the EP group (P < 0.05). CONCLUSION: This experimental study revealed that CAPE administration significantly prevented alveolar bone loss and stimulated periodontal tissue healing.