The aim of this study was to demonstrate the safety and efficacy of H2-saline infusion for treatment of rheumatoid arthritis (RA). We conducted a randomized, double-blind, placebo-controlled investigation of the infusion of 1 ppm H2-dissolved saline (H2-saline) in 24 RA patients. Patients were randomized 1:1 to receive 500 ml of either H2-saline or placebo-saline, which was drop infused intravenously (DIV) daily for 5 days. The disease activity score in 28 joints (DAS28) was measured at baseline, immediately post infusion, and after 4 weeks. Therapeutic effects of H2-saline on joint inflammation were estimated by measuring serum biomarkers for RA, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and urinary 8-hydroxydeoxyguanosine (8-OHdG). In the H2-infused group, average DAS28 decreased from 5.18 ± 1.16 to 4.02 ± 1.25 immediately post infusion and reached 3.74 ± 1.22 after 4 weeks. No significant decrease in DAS28 was observed in the placebo group throughout the study. IL-6 levels in the H2 group significantly decreased in 4 weeks by 37.3 ± 62.0% compared to baseline, whereas it increased by 33.6 ± 34.4% in the placebo group. TNFα levels did not change remarkably in the H2 or placebo groups in 4 weeks post-infusion compared to baseline. The relative ratio of 8-OHdG in the H2 group also significantly decreased by 4.7%. After 4 weeks, MMP3 was significantly reduced by 19.2% ± 24.6% in the H2 group, and increased by 16.9% ± 50.2% in the placebo group. Drop infusion of H2 safely and effectively reduced RA disease activity.
ABSTRACT. A simple method of lymphography of the thoracic duct was investigated. Using three female beagles, contrast media were administered rectally, vaginally and into the perianal tissue. The administration sites were gently massaged, and imaging was carried out at constant intervals using computed tomography and radiograph. Moreover, Indian ink was administered into the rectum mucous membrane in dogs for proof of this method of lymphography, and the lymph drainage routes were observed. The investigation showed that clear computed tomography and radiographic contrast images of the thoracic duct were obtained by subcutaneous and submucosa injection of angiography contrast medium and 3D processing of these images revealed the three-dimensional positions and course of the thoracic duct and cisterna chyli. Chylothorax is a condition in which chyle leaks into the thoracic cavity and accumulates. Symptoms include respiratory impairment, weight loss and exercise intolerance. In most cases, the etiology is unknown [4]. A number of medical and surgical treatments are currently suggested for the treatment of chylothorax. In many cases, because medical therapies are unable to resolve chylothorax completely, surgical treatment must ultimately be considered. To date, surgical treatment of chylothorax has included thoracic duct ligation [2], pleuroperitoneal shunting [11], thoracic omentalization [8], cisterna chyli ablation [6] and pericardiectomy [5], either alone or in combination with thoracic duct ligation. Thoracic duct ligation is recommended as the 1st choice among these methods [3,5]. One possible cause for the failure of thoracic duct ligation and subsequent recurrence is the occurrence mistakes in the surgery itself, such as failure to tie all of the complex tributaries into which the thoracic duct divides [1]. The thoracic duct in dogs is known to form either a single duct or multiple tributaries within the thoracic cavity after passing through the aortic hiatus, and their courses also display a complex morphology [7]. The position and course of the thoracic duct and cisterna chyli must be confirmed preoperatively when thoracic duct ligation or cisterna chyli ablation is performed, for which lymphography of the thoracic duct is of course required [1]. Current methods for performing lymphography of the thoracic duct involve the injection of contrast medium into the mesenteric lymph nodes during laparotomy under anesthesia or contrast imaging of the thoracic duct after the injection of contrast medium into the popliteal lymph node of a pelvic limb [2, 9, 10]. However, laparotomy is an invasive procedure, and reliable results cannot be obtained by percutaneous penetration of lymph nodes when the size and position of these lymph nodes are undetermined. In the present study, beagles were used to investigate new simple sites for administration of contrast media and for obtaining lymphographic images by computed tomography (CT) or radiography of the thoracic duct, which will have clinical applicability.Three healthy ...
Psoriasis, a chronic inflammatory skin disease, is caused by infiltrating lymphocytes and associated cytokines, including tumor necrosis factor (TNF)α, interleukin (IL)-6, and IL-17. Effective treatments, including pathogenesis-based biological agents against psoriasis, are currently under development. Although the role of reactive oxygen species (ROS) in the pathogenesis of psoriasis has been investigated, it remains to be fully elucidated; ROS-targeted therapeutic strategies are also lacking at present. Therefore, the objective of the present study was to assess whether H2, a ROS scavenger, has a therapeutic effect on psoriasis-associated inflammation by reducing hydroxyl radicals or peroxynitrite in the immunogenic psoriasis cascade. Three methods were used to administer H2: Drop infusion of saline containing 1 ppm H2 (H2-saline), inhalation of 3% H2 gas, and drinking of water containing a high concentration (5-7-ppm) of H2 (high-H2 water). Treatment efficacy was estimated using the disease activity score 28 (DAS28) system, based on C-reactive protein levels, and the psoriasis area and severity index (PASI) score, determined at baseline and following each H2 treatment. Furthermore, levels of TNFα, IL-6, and IL-17 were analyzed. The DAS28 and PASI score of the three patients decreased during H2 treatment, regardless of the administration method. The psoriatic skin lesions almost disappeared at the end of the treatment. IL-6 levels decreased during H2 treatment in Case 1 and 2. IL-17, whose concentration was high in Case 1, was reduced following H2 treatment, and TNFα also decreased in Case 1. In conclusion, H2 administration reduced inflammation associated with psoriasis in the three cases examined and it may therefore be considered as a treatment strategy for psoriasis-associated skin lesions and arthritis.
ABSTRACT. Lymph drainage routes from the abdominal and pelvic cavities in beagle dogs were observed serially by following the time course of India ink administered intraperitoneally. Four systems of lymph drainage routes from the peritoneal cavity were observed in this study. The earliest drainage returned to the cranial mediastinal lymph nodes via the sternal lymph vessels; subsequently, the sternal lymph nodes located along the internal thoracic artery became involved. Then, a drainage route via the lymph vessel along the left vagus nerve was observed. The final drainage route flowed into the lateral lymph vessel through the thoracic duct located on the vertebra. These results show that India ink is absorbed from the peritoneal cavity, and that the lymph drainage first flows mainly towards the cranial mediastinal lymph nodes through the ventral lymphatic channels. Our serial observations suggest that, over time, the lymph drainage routes changed from the ventral abdominal to the dorsal thoracic lymphatic channels in the thorax. KEY WORDS: beagle dog, lymph drainage, peritoneal cavity.J. Vet. Med. Sci. 68(11): 1143-1147, 2006 The lymphatic system establishes a lymphatic circulation and transports lymph containing lipid droplets, immunocytes, and tumor cells. Ultimately, lymphatic drainage routes flow into the systemic circulation. However, parts of the lymphatic system are located in serous cavities. These lymphatic routes have yet to be adequately clarified. Previously, a limited amount of information about the lymphatic drainage from the abdominal cavity was collected by examining the route that drains lymph from the canine peritoneal cavity [6]. Tracing marker administered into the peritoneal cavity was found to travel via the diaphragm to the sternal lymphatics located in the ventral inner-wall of the thoracic cavity. Subsequently, the same drainage pattern was observed in many animals [4,7,9]. This lymphatic drainage route may be clinically useful in predicting the course of intraperitoneal cancer dissemination. The present paper provides a detailed description of lymph drainage routes over time following the intraperitoneal administration of India ink in beagle dogs. MATERIALS AND METHODSThree adult male beagle dogs (body weight, 8.5 kg) and one adult female beagle dog (body weight, 6.7 kg) were used for this experiment.Using a fine needle, the male dogs were all injected intraperitoneally with warm India ink dissolved in physiological saline at a dose of 25 ml per kg body weight; the India ink was injected into the pelvic cavity via the rectum in the female dog. The male dogs were sacrificed by an overdose of Nembutal (0.2 ml/kg) at 30 min, 60 min, and 2.5 hr after ink injection, respectively. The female dog was sacrificed at 2.5 hr. A fixative solution [24 (ethylene glycol): 8 (phenol): 1 (formaldehyde solution): 16 (methanol)] was immediately injected intraperitoneally and intrapelvically after the animals were sacrificed. The peritoneal and pelvic cavities were dissected from the carcasses, and these ...
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