Tumor inhibiting properties of stereoisomeric [1,2-bis(3-hydroxyphenyl) ethylenediamine]dichloroplatinum(II)-complexes, Part II: Biological properties

The activity of stereoisomeric [1,2-bis(3-hydroxyphenyl)ethylenediamine] dichloroplatinum(II)-complexes (1-PtCl2,R,S; 2-PtCl2, R,R/S,S; 3-PtCl2, R,R; 4-PtCl2, S,S) on several tumor models (MDA-MB 231 breast cancer cell line; P 388 leukemia, mouse; L 1210 leukemia, mouse; L 5222 leukemia, rat; Ehrlich ascites tumor, mouse--wildtype; cisplatin-, etoposide-, cyclophosphamide-, and daunomycin-resistant, resp.) is described. For comparison the analogous [1,2-bis(4-hydroxyphenyl)ethylendiamine]dichloroplatinum (II)-complexes (5-PtCl2, R, S; 6-PtCl2, R,R/S,S; 7-PtCl2, R,R; 8-PtCl2, S,S) and cisplatin are used. 1-PtCl2 to 4-PtCl2 (OH in 3,3'-positions) show their maximum antitumor effect at lower doses than 5-PtCl2 to 8-PtCl2 (OH in 4,4'-positions). 2-PtCl2 and 6-PtCl2 (R,R/S,S) are more active than 1-PtCl2 and 5-PtCl2 (R,S). 4-PtCl2 and 8-PtCl2 (S,S) are superior to 3-PtCl2 and 7-PtCl2 (R,R). On the L 5222 leukemia 2-PtCl2 (R,R/S,S), 4-PtCl2 (S,S) and 8-PtCl2 (S,S) markedly surpass cisplatin. Strong effects are produced by 2-PtCl2 to 4-PtCl2 on the Ehrlich ascites tumor (wildtype, cisplatin-, etoposide-, cyclophosphamide-, and daunomycin-resistant, resp.). The combination of 4-PtCl2 with cisplatin results in a weakly synergistic effect.     

Investigation of the negative chronotropic action of SK&F 86466 in the pithed normotensive rat

SK&F 86466, 6-chloro-3-methyl-2,3,4,5-tetrahydro-1-H-3-benzazepine, is a potent and selective antagonist of the α₂-adrenoceptor in vitro. This compound produced a small pressor response accompanied by a marked bradycardia when administered i.v. to the pithed normotensive rat. The pressor response was not affected by reserpine treatment, pretreatment with α- or β-adrenoceptor antagonists, atropine, or hexamethonium. The bradycardia was markedly reduced by bilateral vagotomy and pretreatment with atropine and attenuated by hexamethonium. The negative chronotropic action of SK&F 86466 was abolished by a combination of vagotomy and atropine. Mediation of the bradycardia by a baroreceptor reflex was ruled out by the observations that a lack of change in heart rate was associated with the vasopressor response to phenylephrine in the pithed rat pretreated with propranolol. It is concluded that the negative chronotropic action of SK&F 86466 in the pithed rat is mediated indirectly by activation of the cholinergic innervation of the heart.     

Apoptosis: understanding the new molecular pathway.

Advances in science have increased the knowledge of how cells die in the body (apoptosis). A basic understanding of this process can improve nurses' ability to review new scientific literature and enable them to provide safer bedside care.     

Interferon-gamma knockout fails to confer protection against obliteration in heterotopic murine tracheal allografts.

BACKGROUND: Interferon-gamma, produced by T-helper cells, activates macrophages and increases expression of major histocompatibility complex (MHC) products in acute and chronic rejection. We investigated the role of interferon-gamma in murine heterotopic tracheal allografts. METHODS: Tracheas from BALB/c mice were heterotopically transplanted to BALB/c (12 isografts: 2 weeks [n = 6] and 4 weeks [n = 6], C57BL/6 (12 allografts: 2 weeks [n = 6] and 4 weeks [n = 6]) and C57BL/6 interferon-gamma knockout mice (12 interferon-gamma knockout allografts: 2 weeks [n = 4] and 4 weeks [n = 8]). BALB/c interferon-gamma knockout tracheas were transplanted to C57BL/6 mice (reverse knockout: 4 weeks [n = 6]) and BALB/c interferon-gamma knockout mice (4 weeks [n = 2]). C57BL/6 tracheas were transplanted to Bm12 mice (MHC Class II mismatch allografts: 4 weeks [n = 6]). Conventional histology and immunohistochemistry for CD4, CD8 and CD11b were performed. RESULTS: Minimal (<20%) obliteration was seen at 2 weeks in the allograft groups. No obliteration was seen in the isograft groups. However, all allografts were completely obliterated at 4 weeks. Interferon-gamma knockout allograft combinations displayed severe rejection characterized by intense intra- and extraluminal infiltration by CD4-, CD8- and CD11b-labeled cells. The MHC Class II mismatch allograft group showed normal epithelium and mild sub-epithelial infiltration by CD4+ cells at 4 weeks (CD8-, CD11b-). CONCLUSIONS: Absence of interferon-gamma does not protect the allograft from obliteration. Epithelial destruction by cytotoxic T cells appears to be an important mechanism in the development of obliteration in murine heterotopic tracheal allografts.     

Complications associated with the use of the GlideScope® videolaryngoscope

PURPOSE: Two cases are presented wherein the GlideScope videolaryngoscope (GVL) facilitated laryngeal exposure and successful endotracheal intubation, but resulted in pharyngeal injury. CLINICAL FEATURES: GlideScope videolaryngoscopy was performed in two female patients, whose airways were anticipated to present difficulties for direct laryngoscopy. In the first case, following induction of anesthesia, moderate difficulty was encountered in directing the endotracheal tube (ETT) into the patient's larynx. In the second case, minimal difficulty with the GVL was experienced, and no problems were identified with airway instrumentation until the drapes covering the patient's face were removed. In both instances, the ETT had passed through the right palatopharyngeal arch, requiring suturing in the first patient, and electrocautery in the second patient. CONCLUSION: There have been no previously published reports of injuries related to GlideScope laryngoscopy, but perforation of the palatopharyngeal arch occurring in two patients demonstrates a rare but potentially important complication of the GVL. Strategies to minimize this complication are considered.