Biomedical subjects

M W Wichmann

Publications and source records attributed to M W Wichmann.

41 records · Page 3Linked to original sources

PubMed1996

Prolactin: a novel and safe immunomodulating hormone for the treatment of immunodepression following severe hemorrhage.

Recent studies have shown that the anterior pituitary hormone prolactin, together with various cytokines, plays an important role in maintaining normal immune responses. Although there is evidence that prolactin may be a significant immunotropic hormone that can counteract the immunosuppressive effects of drugs such as cyclosporine, morphine, or glucocorticoids, it remains unknown whether prolactin administration has any salutary effects on the depressed immune responses following severe hemorrhage. To study this, mice were bled to and maintained at a mean arterial pressure of 35 mm Hg for 60 min, then adequately resuscitated and segregated into two groups. One group received saline-vehicle (hem-SS); animals in the other group were treated with prolactin (hem-PRL) (100 micrograms per 25 g BW, subcutaneously) immediately before resuscitation. Two hours following saline or prolactin injection, splenocytes (SPL) were harvested and assessed for proliferative capacity (PC) and their ability to release IL-2 and IL-3. Supernatant lymphokine levels were determined by bioassay. The proliferative capacity of the splenocytes, as well as their ability to release IL-2 and IL-3, was significantly depressed in the vehicle-treated hemorrhaged animals, compared to shams. Treatment with prolactin restored the depressed splenocyte functions seen after severe hemorrhage. These results support the notion that the immunosuppression following hemorrhage and trauma may be mediated by hormones from the hypothalamic-pituitary-adrenal axis. Furthermore, our results suggest that the use of prolactin, which did not produce any adverse hemodynamic effects, represents a novel and safe immunomodulating hormone for the treatment of immunodepression following severe blood loss.

Animals↗

PubMed1996

Melatonin administration attenuates depressed immune functions trauma-hemorrhage.

The pineal hormone melatonin has been used in clinical trials in patients suffering from AIDS and also as an adjuvant for cancer therapy. Although melatonin has been reported to have beneficial effects in some animal models of immune dysfunction, it remains unknown whether this hormone has any salutary effects on immunity following soft-tissue trauma and/or major blood loss. To study this, soft-tissue trauma (2.5-cm midline laparotomy) and hemorrhagic shock (arterial BP 35 +/- 5 mm Hg) were induced in C3H/HeN mice. The mice were resuscitated after 90 min of hypotension with the shed blood and lactated Ringer's solution. Treatment with saline, vehicle, or melatonin (10 mg/kg BW) subcutaneously was administered in the evening of the day of surgery and again on the following evening. All animals were sacrificed at 48 hr following trauma-hemorrhage and resuscitation to obtain plasma, splenocytes, as well as splenic and peritoneal macrophages (Mphi). The results indicate that melatonin administration after trauma-hemorrhage significantly improved the depressed immune functions, as evidenced by the restoration of Mphi IL-1 and IL-6 release, as well as significantly improved splenocyte IL-2 and IL-3 release and splenocyte proliferative capacity. No differences in circulating corticosterone levels between vehicle- and melatonin-treated animals were observed. This is the first study to show that melatonin, which is reported to be free of adverse side effects, can be considered a safe and effective therapeutic agent for restoring the depressed immunological function after soft-tissue trauma and hemorrhagic shock.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Melatonin administration following hemorrhagic shock decreases mortality from subsequent septic challenge.

Melatonin administration has been reported to have beneficial effects on immune function in some clinical studies and in several animal models of immune dysfunction. Furthermore, recent studies suggest beneficial effects of melatonin on depressed immune function following trauma-hemorrhage. Nonetheless, it remains unknown whether this hormone has any salutary effects on survival following hemorrhagic shock and subsequent septic challenge. Male C3H/HeN mice were bled to and maintained at a mean arterial blood pressure of 35 +/- 5 mm Hg for 90 min, adequately resuscitated, and 48 hr thereafter subjected to sepsis (cecal ligation and puncture; CLP). Melatonin-treated mice received either short-term treatment on Days 1 and 2 after hemorrhage or continuous treatment throughout the study. Treatment with vehicle (10% ethanol in normal saline) or melatonin (10 mg/kg body weight) was administered daily starting in the evening of the day of hemorrhage/sham-operation. Short-term melatonin administration after hemorrhage significantly improved survival in animals subjected to septic challenge. Continuous melatonin treatment did not improve survival, as compared to vehicle-treated mice subjected to shock and CLP. Moreover, continuous melatonin treatment in sham-operated animals significantly increased mortality compared to short-term-treated and vehicle-treated animals. While the mechanisms of the differential effects of melatonin administration are yet to be clearly defined, this study, nonetheless, demonstrates the salutary effects of short-term melatonin administration in the treatment of immune dysfunction following hemorrhagic shock.

Animals↗

PubMed1996

Depressed osteoblast activity and increased osteocyte necrosis after closed bone fracture and hemorrhagic shock.

BACKGROUND: Although bone fracture and hemorrhagic shock are frequent complications in trauma patients, it remains unknown whether hemorrhagic shock after bone fracture produces any deleterious effects on osteoblast function and osteocyte necrosis. METHODS: Sham-operation, closed bone fracture (right tibia) with and without hemorrhagic shock (mean arterial blood pressure 35 +/- 5 mm Hg for 90 minutes followed by fluid resuscitation) were induced in 18 male C3H/HeN mice (25 g body weight) At 72 hours after the experiment, all animals were killed, whole blood was obtained by cardiac puncture, and plasma assayed for circulating levels of osteocalcin. RESULTS: Plasma osteocalcin levels were found to be significantly depressed after closed bone fracture in conjunction with hemorrhagic shock. Closed bone fracture alone increased plasma osteocalcin. Histologic analysis of the fracture sites revealed that hemorrhagic shock after closed bone fracture significantly increased osteocyte necrosis adjacent to the fracture site, when compared to animals with closed bone fracture alone. CONCLUSIONS: These findings suggest that severe hemorrhage after closed bone fracture depresses osteoblast activity and increases osteocyte necrosis, which should compromise fracture healing under those conditions.

Animals↗

PubMedDate not supplied

Carcinoembryonic antigen for the detection of recurrent disease following curative resection of colorectal cancer.

BACKGROUND: During recent years a discussion about cost-effectiveness and importance of follow-up determination of carcinoembryonic antigen (CEA) after curative resection of large bowel cancer has developed. PATIENTS AND METHODS: Between 1990 and 1998 follow-up CEA levels of 1,321 patients after curative colorectal cancer resection were prospectively collected in cooperation with family physicians, CEA determinations were made with different assays by various laboratories. The reported findings were adjusted for the different methods used. RESULTS: 306 patients developed recurrent disease following curative cancer resection (23.2% of all patients). Regarding the role of follow-up CEA determination, they were divided into: I. no preoperative CEA determination/insufficient follow-up (N = 47); II. no elevation of CEA with primary cancer, a) elevation with recurrent disease (N = 62), b) no elevation at any time point (N = 53), c) role of CEA not completely elucidated (N = 41); III. elevated CEA levels with primary cancer, a) no increase with recurrent disease (N = 21), b) increase with other symptoms of recurrent disease (N = 45), c) increased levels as early symptom of recurrent disease (N = 37). 30 patients (9.8% of all patients with recurrent disease; 2.3% of all patients) with increased CEA levels at the time of recurrent disease underwent surgical resection with curative intention (R0 resection). CONCLUSIONS: Our findings indicate that up to 47% of the patients with recurrent disease and 11% of all patients (N = 144, groups IIa + IIIb + IIIc) could benefit from routine follow-up CEA determinations after curative colorectal cancer resection. Nonetheless, only 2.3% of all patients with elevated CEA levels underwent R0 resection of recurrent disease. Despite these detection and R0 resectability rates, CEA plays a crucial role in the early detection of recurrent disease and remains an important part of routine patient care after curative resection of colorectal cancer.

Biomarkers, Tumor↗