In vitro anticancer activity of Betulinic acid and derivatives thereof on equine melanoma cell lines from grey horses and in vivo safety assessment of the compound NVX-207 in two horses.

Betulinic acid, a pentacyclic triterpene, and its derivatives are promising compounds for cancer treatment in humans. Melanoma is not only a problem for humans but also for grey horses as they have a high potential of developing melanoma lesions coupled to the mutation causing their phenotype. Current chemotherapeutic treatment carries the risk of adverse health effects for the horse owner or the treating veterinarian by exposure to antineoplastic compounds. Most treatments have low prospects for systemic tumor regression. Thus, a new therapy is needed. In this in vitro study, Betulinic acid and its two derivatives B10 and NVX-207, both with an improved water solubility compared to Betulinic acid, were tested on two equine melanoma cell lines (MelDuWi and MellJess/HoMelZh) and human melanoma (A375) cell line. We could demonstrate that all three compounds especially NVX-207 show high cytotoxicity on both equine melanoma cell lines. The treatment with these compounds lead to externalization of phosphatidylserines on the cell membrane (AnnexinV-staining), DNA-fragmentation (cell cycle analysis) and activation of initiator and effector caspases (Caspase assays). Our results indicate that the apoptosis is induced in the equine melanoma cells by all three compounds. Furthermore, we succeed in encapsulating the most active compound NVX-207 in 2-Hydroxyprolyl-ß-cyclodextrine without a loss of its activity. This formulation can be used as a promising antitumor agent for treating grey horse melanoma. In a first tolerability evaluation in vivo the formulation was administered every one week for 19 consecutive weeks and well tolerated in two adult melanoma affected horses.

Testicular circulatory isolation: not a cause of immune-mediated testis injury in the rat.

BACKGROUND: Testicular circulatory isolation (TCI), a regional drug exclusion approach designed to prevent chemotherapy-induced male infertility, can reduce testicular drug exposure and preserve fertility. The immunological sequelae of this surgical procedure were investigated. METHODS: Forty Sprague-Dawley rats received unilateral TCI for 45 min and were killed at intervals of up to 43 days later. Testicular histology was evaluated qualitatively using hematoxylin and eosin stain, a direct immunofluorescent technique for detection of antigen-antibody complexes, and an indirect immunofluorescent technique to detect circulating antitestis antibodies. RESULTS: No immune-mediated injury was evident up to 43 days after TCI. CONCLUSION: The current work, taken together with previously published data, indicate that TCI produces no immunological damage in the rat testis. Because TCI is well tolerated in humans, this work also supports the institution of human clinical trials of this technique in men about to receive fertility-threatening chemotherapy.

Laparoscopic restoration of intestinal continuity after Hartmann procedure.

Two cases of laparoscopic restoration of intestinal continuity are presented. The procedures were technically straightforward and both patients did well. These cases add to a small but growing literature documenting the technical feasibility of laparoscopic intestinal surgery. The potential risks and benefits of this minimally invasive technique are discussed.

Preservation of fertility following doxorubicin administration in the rat.

Several hundred thousand men receive chemotherapy each year; many are sterilized by this treatment. Testicular circulatory isolation (TCI), a regional drug exclusion approach to circumvent chemotherapy-related infertility, lessens doxorubicin-induced testicular injury in the rat. We evaluated the effect of TCI on doxorubicin-induced infertility in this study. Thirty-two eight-week-old male Sprague-Dawley rats were used. Eight rats received TCI for 45 min. Eight received doxorubicin (i.v. bolus) plus sham surgery. Eight received i.v. doxorubicin given immediately after institution of TCI. Eight controls received sham surgery alone. Mating studies began 2 months later. Six of the 8 males receiving TCI alone were fertile. In the doxorubicin-treated, sham-operated group, 0 of 7 animals were fertile. In the doxorubicin-treated group which also received TCI, 2 of 7 males were fertile. In the sham-operated group, all 8 rats were fertile. This is the first evidence that regional drug exclusion technique can improve fertility in this model.

Laparoscopic cholecystectomy in anticoagulated patients.

Although minimally surgically invasive, laparoscopic surgery has yet to be proven safe in patients receiving anticoagulants. Retrospectively, the laparoscopic management of four patients requiring anticoagulation for cardiac valvular prostheses or chronic atrial fibrillation was reviewed with regard to potential hemorrhagic complications. Warfarin was discontinued preoperatively in all cases. Heparin anticoagulation was individualized according to each patient's risk for thrombosis. Laparoscopic cholecystectomy and intraoperative cholangiography were completed in each patient without resulting hemorrhagic complications. The operative management of patients exhibiting cholecystitis may be complicated by anticoagulation therapy required for preexisting conditions/diseases such as cardiac valve prostheses, chronic atrial fibrillation, deep venous thrombosis, and pulmonary embolism. The minimally invasive nature of laparoscopic surgery lends itself well to cholecystectomy required in the face of anticoagulation treatment. This limited initial series of selected patients demonstrates the feasibility and efficacy of laparoscopic cholecystectomy in patients receiving anticoagulants.