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.     

Prevalence of traumatic injuries to the permanent incisors in candidates for orthodontic treatment

Abstract  – The dental records made on presentation of 1367 consecutive patients (731 females and 636 males) for orthodontic treatment at a private orthodontic practice between 1998 and 2002 were examined for data relating to trauma to the permanent incisors. The results showed that 10.3% of these patients had suffered from dental trauma before the onset of orthodontic treatment. The highest prevalence of dental trauma was determined in the 11–15 years age group, corresponding to the dental developmental stage of the late mixed dentition. The most frequently affected teeth were the maxillary central incisors (79.6%), and the most common types of trauma were fracture of enamel–dentin without pulpal involvement (42.7%) and fracture of enamel (33.8%). Compared to patients with normal overjet and adequate lip coverage, the frequency of dental trauma was significantly higher in patients with increased overjet and adequate lip coverage ( P  = 0.028) or with increased overjet and inadequate lip coverage ( P  = 0.003). The results of the present study indicate that a significant percentage of candidates for orthodontic treatment, and especially those with increased overjet and inadequate lip coverage, suffer trauma to their permanent incisors before the onset of orthodontic treatment. It might also be concluded that preventive orthodontic treatment of such patients should be initiated and completed before the age of 11, i.e. in the early to middle mixed dentition.     

Lipid-drug conjugate nanoparticles of the hydrophilic drug diminazene-cytotoxicity testing and mouse serum adsorption.

Sleeping sickness is a widely distributed disease in great parts of Africa. It is caused by Trypanosoma brucei gambiense and rhodiense, transmitted by the Tse-Tse fly. After a hemolymphatic stage, the parasites enter the central nervous system where they cannot be reached by hydrophilic drugs. To potentially deliver the hydrophilic antitrypanosomal drug diminazene diaceturate to the brain of infected mice, the drug was formulated as lipid-drug conjugate (LDC) nanoparticles (NP) by combination with stearic- (SA) and oleic acid (OA). To estimate the in vivo compatibility, the particles were incubated with human granulocytes. Because as potential delivery mechanism the absorption of specific serum proteins (ApoE, Apo AI and Apo AIV) was found to be responsible for the delivery of nanoparticles to the brain, demonstrated using PBCA nanoparticles coated with polysorbate 80 (LDL uptake mechanism) the nanoparticles were incubated with mouse serum and the adsorption pattern was determined using the 2-D PAGE technique. As a result of this study, the cytotoxic potential was shown to decrease when diminazene is part of the particle matrix compared to pure fatty acid nanoparticles and the mouse serum protein adsorption pattern differs from the samples studied earlier in human serum. Especially, the fact concerning Apo-E that could be detected when the particles were incubated in human serum is absent after the mouse serum incubation, potentially, is a critical point for the delivery via the LDL-uptake mechanism but the data demonstrate that LDC nanoparticles, with 33% (wt/wt) drug loading capacity possess the potential to act as a delivery system for hydrophilic drugs like diminazene diaceturate and that further studies have to demonstrate the usability as a brain delivery system.     

Treatment of cremaster synkinesias with botulinum toxin A: a video case report.

Synkinesias secondary to nerve lesions and aberrant re-innervation are well-known phenomena especially after lesions of the facial nerve. Synkinesias can successfully be treated with botulinum toxin A (BTx A). Synkinesias of the cremaster muscle have not been described or treated to date. We present the case of a 62-year-old man who developed synkinesias of both cremaster muscles after extensive laparatomy for esophageal cancer. Treatment of synkinesias with various oral medications had been unsuccessful. Electromyography-guided injections of BTx A in both cremaster muscles (15 MU on the right and 10 on the left) led to significant symptom relief for an average of 8 weeks. We present the case including pre- and posttreatment video clips.     

Cigarettes, alcohol and marijuana are related to pyospermia in infertile men

The relationship of current use of cigarettes, marijuana and alcohol to the parameters of seminal fluid analysis, sperm penetration assay and sperm autoimmunity was studied in 164 men from infertile couples. Current cigarette smokers, marijuana users and heavy alcohol users showed greater numbers of leukocytes in the seminal fluid than did nonusers (p less than 0.02, less than 0.007 and less than 0.01, respectively). In addition, cigarette smokers had lower sperm penetration assay scores than nonsmokers (median 2.5 versus 8.0, p = 0.05). Users of cigarettes, marijuana or alcohol showed no decrease in sperm count, motility or percentage of oval sperm, and no difference in prevalence of antisperm antibodies compared to nonusers. After controlling for past sexually transmitted diseases and multiple substance exposures in a multivariate model, use of cigarettes (p = 0.006), marijuana (p = 0.12) or alcohol (p = 0.098) continued to be associated with a trend toward increased number of seminal fluid leukocytes. Cigarette smoking continued to show a significant decrease in sperm penetration assay score (p = 0.03).     

Trimipramine: A challenge to current concepts on antidepressives

Although it is chemically a classical tricyclic antidepressant agent, trimipramine shows atypical pharmacological properties. Its well-documented antidepressant action cannot be explained by noradrenaline or serotonin reuptake inhibition or by a down-regulation of β-adrenoceptors. Furthermore, its receptor affinity profile resembles more that of clozapine, a neuroleptic drug, than that of tricyclic antidepressants. Trimipramine does not reduce, but rather increases, rapid eye movement sleep. It stimulates nocturnal prolactin secretion and inhibits nocturnal cortisol secretion, and may act at the level of the hypothalamus on corticotropin-releasing hormone secretion. Trimipramine is of particular value in depressed patients with insomnia, and it has been shown to be effective in the therapy of primary insomnia. As the pharmacological profile indicates, and an open clinical study has shown, trimipramine might also be active as an antipsychotic. The drug is both a tool for increasing our understanding of depression and a potential therapy for several psychiatric disorders.     

Decision making and results in subtotal and total lower leg amputations: Reconstruction versus amputation

As a result of modern therapeutic and technological advances, the surgeon has the ability to salvage even the most severely injured lower limbs. However, the success of replantation nowadays is no longer measured simply on the basis of restoration of viability but also on functional outcome compared with primary amputation with early prosthetic fitting, the risk to the patient during and after replantation and the overall time of treatment which should not exceed 2 years. Although every major limb replantation has to be considered individually, the decision-making process for reconstruction (replantation/revascularisation) versus amputation with subsequent early prosthetic fitting should be determined by objective criteria. Based on personal experience and an extensive literature search, an algorithm for treatment of amputation or amputation-like injuries to the lower leg has been developed and tested in a clinical study. A 100% viability success rate was achieved. There was not only a significant increase in the percentage of “functional extremities” but also a doubling in grade I results. Moreover, there was a 50% reduction in patients presenting a “non-functional extremity”, and no patient required a secondary re-amputation. The replantation risk (e.g., risk of severe systemic disturbance during and/or after replantation) was about 16.6% (2/12) in our study. There was a significant decrease in the postoperative complication rate and no patient died during or after replantation. Based on our experience, if reconstruction in subtotal or total lower leg amputation is done for a well-selected patient group, good functional results with a reasonable replantation risk and a reasonable time for social re-integration can be achieved. © 1995 Wiley-Liss, Inc.     

Bone-ligament transfer of coracoacromial ligament for acromioclavicular dislocation: A new fixation method used in 6 cases

We treated 6 grade III acromioclavicular injuries with a new fixation method using a bone-ligament transfer of the coracoacromial ligament into a clavicular tunnel. After an average of 16 months, function and cosmesis were excellent in all patients.