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Aim: To evaluate and compare the pH and antibacterial property of Ca(OH) 2 combined with iodine potassium iodide (IKI) or chlorhexidine (CHX) on E. faecalis and to assess and compare their effect on fracture resistance of root dentin. Materials and Methods: CHX (0.5%) The following test materials were used: Group I Calcium hydroxide + saline, Group II Calcium hydroxide + CHX (0.5%) and Group III Calcium hydroxide + IKI (2%). For antibacterial activity, 60 root dentin blocks (20 in each group) were infected by E. faecalis followed by placement of medicaments. At the end of 24 h and 7 days, 10 samples from each group were randomly chosen and assessed for antibacterial activity. For evaluation of root strength, 30 teeth were used and stored in sterile saline after placement of medicament. At the end of 30 days, samples were subjected to fracture resistance testing on the Universal Strength Testing Machine. Hounsfield strength testing machine, UK pH of the various calcium hydroxide combinations was determined with a digital pH meter. Statistical analysis : Kruskal Wallis test, Mann Whitney U test, and one-way ANOVA test for intergroup comparison and Wilcoxon′s signed rank test and student′s paired t test for intragroup comparison. Results : Group III showed significantly greater antibacterial activity against E. faecalis, followed by group II and control group. There was no statistically significant change in the pH and root strength values among all the groups. Conclusion : The present study revealed that IKI or CHX in combination with Ca(OH)2 is an effective medicament against E. faecalis.

Objective : To evaluate and compare the efficacy of conventional and digital radiographic methods in the detection of simulated external root resorption cavities and also to evaluate whether the detectability was influenced by resorption cavity sizes. Methods : Thirty-two selected teeth from human dentate mandibles were radiographed in orthoradial, mesioradial and distoradial aspect using conventional film (Insight Kodak F-speed; Eastman Kodak, Rochester, NY) and a digital sensor (Trophy RVG advanced imaging system) with 0.7mm and 1.0mm deep cavities prepared on their vestibular, mesial and distal surfaces at the cervical, middle and apical thirds. Three dental professionals, an endodontist, a radiologist and a general practitioner, evaluated the images twice with a one-week time interval. Results : No statistical significance was seen in the first observation for both conventional and digital radiographic methods in the detection of simulated external root resorptions and for small and medium cavities but statistical difference was noted in the second observation (P< 0.001) for both the methods. Conclusion : Considering the methodology and the overall results, conventional radiographic method (F-speed) performed slightly better than the digital radiographic method in the detection of simulated radiographic method but better consistency was seen with the digital system. Overall size of the resorption cavity had no influence on the performance of both methods and suggests that initial external root resorption lesion is not well-appreciated with both the methods as compared to the advanced lesion.

Objectives : Orofacial manifestations (OFMs) are seen early in the course of HIV disease in children and can also act as indicators for the presence of the disease. The objective of the study were to find the prevalence of OFMs of HIV in infected children, co-relate them with their CD4 counts and establish whether OFMs could be used as markers for disease progression. Materials and Methods : Using the diagnostic criteria recommended by the European Collaborative Clearinghouse (ECC) on oral problems related to HIV infection and WHO Collaborating Centre on oral manifestations of the HIV, 48 HIV-infected children were examined at the baseline and their CD4 counts were obtained. A follow-up was conducted 6 months later. Chi-Square test was used to analyse the data obtained. Results : OFM showed a high prevalence in HIV-infected children. The degree of immunosuppression was found to co-relate with the presence of OFMs. But, it could not be established that the presence of OFMs could be a marker for HIV disease progression. Conclusion : The results of our study indicated a high prevalence of OFMs in HIV-infected South Indian children. A decline in CD4 counts was found to be associated with more number of OFMs. However, we were unable to establish OFMs as markers for HIV disease progression. The sample size in our study being about 48 patients and the variability in the initiation and duration of HAART therapy, use of other drugs not being considered, may have an influence on the result of our study. Larger population groups, with parameters such as nutritional status and HAART initiation included, can probably give a more conclusive result..

As dental practitioners, we often come across oral ulcerations of varied etiology. Among all the causes of oral ulcers, those due to neutropenia are significant. Neutropenia can occur in many systemic conditions and also in patients on long-term therapy of certain drugs like phenytoin. The diagnosis of neutropenia in time leads to early recognition of the cause of this fatal condition. Here, we report a case of a 50-year-old female patient who developed oral ulcerations secondary to phenytoin-induced neutropenia. Early diagnosis of the condition led to discontinuation of the offending drug and significant improvement in her blood picture and also prevented her from falling prey to many other systemic infections that neutropenia can cause.

Non-Hodgkin′s lymphomas (NHL) constitute a diverse group of lymphoid neoplasm that differ in clinical manifestations, response to therapy and prognosis. Non-Hodgkin′s lymphoma in the mouth, however is less common. When it does occur, it can develop in either osseous or soft tissues of the oral cavity, the most frequent sites being the tonsils, palate and buccal mucosa. Swelling, pain, paresthesia, anesthesia, ulceration and discoloration are common symptoms of oral lymphomas. Non-Hodgkin′s lymphomas commonly affects the elderly and immunosuppressed with a slight predominance in males.

Analytical procedure more advanced allowed to identify, to isolate, and assay the compounds present in propoli which is is developed to be a valuable biological product as food resource as medical resource. Analytical procedure more and more sophisticated allowed (us) to assay the propoli composition without operate the derivatization of phenolic constituents making use the capacity of different detector used. These phenolic contents were analysed by capillary gas chromatography using an electron-capture detector. This detector shown a good electron capture response of these compounds, which belong to the so-called "conjugated electrophores".

Two multivalent immunotoxins (ITs) with cytotoxic potential against Thy 1.2-expressing tumor cells were used in association with mouse interleukin 2 (IL2) for treatment of mice bearing ascitic EL4 lymphomas. The combined treatment, ITs + IL2, induced an enhanced antitumor effect revealed by a significant prolongation of the survival time of mice as compared to the simple treatment with ITs or IL2 alone. According to the survival of mice treated by combined therapy, the proportion of killed tumor cells rose up to 94% as resulted from the dose-dependent curve of the survival of nontreated mice versus the number of tumor cells inoculated.

The protective role of amrinone against toxicity of anthracyclines was examined in both mice and rats. These two anthracyclines were selected since they are characterized by different patterns of toxicity. In contrast to doxorubicin, the 4'-deoxy derivative did not cause delayed mortality. The results of this investigation indicate that amrinone is an effective protective agent against acute lethal events induced by both anthracyclines. However, the inotropic agent did not reduce the delayed mortality produced by doxorubicin. This parallels the apparent lack of prevention of doxorubicin-induced myocardial toxicity in CD rats, as determined by ECG changes and by morphologic alterations following multiple drug administrations. The administration of amrinone did not interfere with the antitumor activity of 4'-deoxy-doxorubicin against C-26 colon tumor.

C57BL/6 mice with EL4 leukemia cells in ascitic form were intraperitoneally treated with ricin A chain-multivalent antibody immunotoxins. The immunotoxins containing rabbit IgG anti-Thy 1.2 antibodies complemented by protein A of Staphylococcus aureus were able to interact specifically with the target cells and to induce an antitumor effect as revealed by an increase in survival time of the mice. No apparent secondary effects consecutive to a cytotoxic action on the normal Thy 1.2 antigen bearing cells were observed with the immunotoxin doses used.

The influence of tumor growth kinetics on response to doxorubicin treatment of C3H mammary carcinoma was investigated. Gompertzian growth curves were obtained for the tumor mass of each mouse by a computerized best fit program. The response was assessed by evaluating: a) the total clonogenic cell reduction as a fraction of the initial tumor volume or the tumor volume that should result at the end of treatment in a free growth condition, and b) the partial clonogenic cell reduction at each drug administration, assuming a first order cell kill hypothesis. Slowly growing tumors at each dose level showed a significantly poorer response than rapidly growing tumors. Each response index exhibited a linear correlation with the specific instantaneous growth rate at the time of treatment. Data also suggested a dose-response dependence.

The main side effect in photodynamic therapy is photosensitization of the patient's skin following systemic administration of the photosensitizing agent. In the case of superficial lesions, this problem can be avoided by topically applying the drug: in this way a local treatment can be performed. We tested the photosensitizing properties of a 2% solution of TPPS (tetrasodium-tetraphenylporphinesulfonate) in a vehicle containing a penetration enhancer, Azone, on skin of nude mice. An aliquot of 0.1 ml/cm2 of the solution was painted on the skin overlying an s.c. implanted NMU-1 tumor. Subsequently, animals were sacrificed at different times after application. Fluorescence microscopy revealed that TPPS penetration depth was related to time elapsed after application and to painting modalities. Solution penetration was enhanced by wiping with ether immediately before painting. Irradiation at 80 mW/cm2 for 20 min with a dye laser emitting at 640 nm, 4 h after TPPS application, produced necrosis of the upper skin layers, up to 0.2 mm in depth. These findings suggest that topical TPPS administration, followed by laser irradiation, may be a suitable treatment modality for skin lesions involving epithelial layers, even though several aspects of this metodology need further investigation.

Administration of amrinone, a new inotropic agent, markedly reduced acute lethal toxicity in normal female Swiss and male BALB/c mice given lethal doses of doxorubicin. Because amrinone abolished the negative inotropic effect of doxorubicin in isolated guinea pig atria, it was suggested that partial protection from acute toxicity of the antitumor antibiotic is directly related to protection of cardiac function.

The investigation has been carried out on stimulated and unstimulated peritoneal cavities of rats. China ink and Corynebacterium parvum were injected i.p. both as peritoneal stimuli and markers. Omenta were picked up at time intervals beginning with 10 min and up to seven days after the i.p. injection. The light and electronmicroscopic investigation showed after 10-30 minutes labeled macrophages stuck as monolayers on some peritoneal areas corresponding to the milky spots which developed in size and number. Days after the i.p. injection the labeled macrophages were found deeper in the milky spots. After the fourth day they appeared in the regional lymph nodes. The milky spots contained also large lymphocytes and plasma cells. The results suggest that milky spots are not only places of resident macrophages development and release in the peritoneal cavity but also their exit pathways. Therefore the omentum leads the traffic of peritoneal macrophages. The developed milky spots play also the role of lymphoid structures providing grounds for macrophage-lymphocyte contacts.

We have investigated the effect of ICRF-159 on the toxicity of daunorubicin (DR) and doxorubicin (DX) given iv, and the effectiveness of ICRF-159 combined with DR or DX on the growth of transplantable MLV-M (murine leukemia virus-Moloney) leukemia, MS-2 solid sarcoma, and pulmonary MS-2 metastases in mice. The injection of ICRF-159 concurrently with the administration of DR resulted in a marked decrease in the toxicity of the antibiotic. However, when DX was injected concurrently with ICRF-159 an increase in antibiotic toxicity was observed, except when ICRF-159 was employed at a very low dosage. ICRF-159 administered alone did not influence the tumor growth in the systems tested and did not result in antimetastatic activity. In mice bearing transplanted MLV-M leukemia, the effects of the combination of ICRF-159 with DR or DX were not superior to those of DR or DX treatment on either tumor growth or lifespan. The treatment of MS-2 tumor with the ICRF-159 and DX combination neither produced a therapeutic synergism (therapeutic response superior to the maximum response obtainable by either agent independently) nor antagonized the antineoplastic action of DX. A marked inhibition of tumor growth and increase in lifespan were observed in the mice treated with a high dose of DR (10 mg/kg/injection) plus ICRF-159 (50 mg/kg/injection). We have also examined, on MS-2 lung metastases, the effectiveness of surgical-adjuvant combination chemotherapy with DR or DX plus ICRF-159 injected at different times with respect to surgery. A synergistic effect of DX or DR with ICRF-159 was observed when the drug treatment was performed before the surgery, or both before and after the surgery. No synergistic effect of DX or DR with ICRF-159 on MS-2 lung metastases was found when the MS-2 lung metastases were treated after the surgery. A higher antimetastatic activity was observed in the groups treated with a combination of toxic doses of DR and ICRF-150 than in the groups treated with a combination of toxic doses of DR and ICRF-159 than in the groups treated with tolerated doses of the antibiotic.

Free growth and post-Doxorubicin treatment regrowth of the C3H mammary carcinoma were analysed in individual mice. In both cases, the Gompertzian function provided a better fit than the exponential function, and the difference was statistically significant (P less than 0.001, chi 2 test). No comprehensive Gompertzian function was found, and each individual tumour growth or regrowth was described by a specific curve. Nevertheless, although both individually measured alpha 0 and beta, Gompertzian parameters varied from one animal to another, in both free-growing and post-treatment regrowing tumours a strong linear correlation between alpha 0 and beta was found. A parallelism test was performed to verify if there exists any treatment-induced alteration. The two regression lines appeared to be identical, however.

4'-Deoxydoxorubicin has been compared with doxorubicin as regards potency, antitumor activity and toxicity in tumored and non-tumored mice treated i.v. according to different schedules. 4'-Deoxydoxorubicin was 1.5-3 times more toxic and more potent than doxorubicin. At equitoxic doses, 4'-deoxydoxorubicin was: as active as doxorubicin against Gross leukemia, mammary carcinoma and MS-2 sarcoma; slightly less active than doxorubicin against B16 melanoma; more active than doxorubicin against colon 38 adenocarcinoma. The best schedule of administration of 4'-deoxydoxorubicin in mice was the weekly treatment. The strong effectiveness against colon 38 adenocarcinoma makes 4'-deoxydoxorubicin a particularly interesting new anthracycline derivative that deserves clinical trials.

The selective inhibitory effect of sodium salicylate (2.5 M) on the adrenal medulla was investigated histopathologically, histoenzymatically, electron microscopically and biochemically. It was proved that the different behaviour of nicotinamide-adenine dinucleotide (NAD) and nicotinamide-adenine dinucleotide phosphate (NADP) linked dehydrogenases under the action of sodium salicylate can account for the survival of cortical cells, while the medullar ones are necrosed.

The new anthracycline glycosides 4-demethoxy-4'-deoxydaunorubicin and 4-demethoxy-4'-O-methyldaunorubicin, synthesized by coupling 4-demethoxydaunomycinone with 1-chloro-derivatives of protected 4-O-methyl and 4-deoxydaunosamine derivatives, have been converted into the corresponding doxorubicin analogs. The new compounds have been compared for antitumor effect with the parent drugs and with the previously described 4-demethoxydaunorubicin, 4-demethoxy-4'-epidaunorubicin, and their doxorubicin analogs. All of the new analogs were more cytotoxic against HeLa cells in vitro and were more toxic and more potent in mice than the parent drugs. Comparison at optimal antitumor doses showed that the new analogs were as active as the parent drugs against ascitic P388 leukemia and disseminated Gross leukemia. They were also active when administered orally. The new doxorubicin analogs were slightly more active than doxorubicin against ascitic L1210 leukemia and were markedly more active against disseminated L1210 leukemia. In a parallel activity-cardiotoxicity test in C3H mice repeatedly treated iv, 4-demethoxydoxorubicin, 4-demethoxy-4'-epidoxorubicin, 4-demethoxy-4'-O-methyldoxorubicin, and 4-demethoxy-4'-deoxydoxorubicin showed antitumor activity against mammary carcinoma without inducing the typical myocardial lesions observed after doxorubicin treatment, 4-Demethoxy-4'-O-methyldoxorubicin, because of its high antitumor effectiveness, lack of cardiac toxicity in mice, and activity by the oral route, deserves further study.

The effectiveness of laser photoradiation therapy with hematoporphyrin derivative sensitization was tested in the MS-2 sarcoma. This solid tumor, transplanted into the pad of the hind leg of BALB/c mice, was found to be a sensitive experimental model for a quantitative evaluation of response to phototherapy and for determination of critical parameters in laser phototherapy treatment. Under our experimental conditions, optimal therapeutic effects appeared to be critically dependent on drug dose, number of treatments, light intensity, and irradiation of the peripheral border of the tumor.

This study assessed the antitumor activity of 1-(2-chloroethyl)-3-/2-(dimethylaminosulfonyl)ethyl-1-nitrosourea (TCNU), a newly soluble nitrosourea, on NMU-1 lung tumor, a transplantable murine model poorly sensitive to BCNU. TCNU delivered orally was more effective after weekly than after biweekly treatments. When TCNU was given weekly intravenously, its therapeutic index was higher than after oral treatment. Compared with BCNU, TCNU showed superior antitumor effects on NMU-1 murine lung tumor. In this experimental model, TCNU activity was comparable to that of drugs active on human lung cancer.

The synthetic polypeptide, poly-L-aspartic acid (PAA, mol. wt = 20,000) has been used as a macromolecular carrier for doxorubicin. The drug may be released in vivo through hydrolysis of the ester linkage formed between the carboxyl groups of the polymer and the drug side chain. PAA has been found to be a suitable carrier since it is a soluble, biodegradable, multivalent and nontoxic polymer. The toxicity and the therapeutic efficacy of free and polymer-linked doxorubicin have been evaluated in normal and tumour-bearing mice, using a variety of experimental tumour systems. In studies on single and multiple drug administration, the results indicated that the polymeric derivative of doxorubicin had approximately 3-fold lower toxicity than did free drug. In addition, the severity of specific toxic effects, including cardio- and vesicant toxicity, were appreciably reduced following conjugation to PAA. The doxorubicin-PAA conjugate gave similar or rather greater therapeutic effects than free drug at less toxic doses. This effect, more evident in the highly sensitive tumours, suggests an improvement of the therapeutic index of the polymer-linked drug.

A mixed platinum (II) complex with tert-butylamine and doxorubicin (coordinated via the amino-group) has been synthesized and tested for antitumor activity. The results indicate that the complex was active against doxorubicin-resistant P388 and cisplatin-resistant L1210 leukemias, while maintaining antitumor activity against sensitive parent lines.

Although the photochemical reaction of hematoporphyrin derivative (HpD) appears to play a major role in cytotoxic activity, the hyperthermal contribution to tumor destruction has not yet been clarified. We investigated its role in the effectiveness of laser photoradiation therapy using MS-2 sarcoma transplanted into the hind pad of BALB/c mice as the experimental model. Mice received HpD i.v., 25 mg/kg - 24 h before exposure to light delivered from a dye laser or Nd-YAG laser, or before warming in a thermostated bath. Since our aim was not to cure the tumor, the treatment response was evaluated only as inhibition of tumor growth at different days after treatment. Our results support the view that in laser photochemotherapy the hyperthermia produced by irradiation and the photodynamic effect mediated by HpD could contribute to tumor destruction. Moreover, a synergistic interaction between the photodynamic effect and heat was observed in this experimental model.

Daunorubicin was bound to poly-L-aspartic acid via the methylketone side chain of the drug to avoid reaction of the sugar amino group believed to be essential for optimal drug activity. Attachment of the drug to the polyamino acid by an ester linkage was achieved by nucleophylic substitution reaction of 14-bromo-daunorubicin. Compared with free daunorubicin, the polymeric derivative was less cytotoxic to HeLa cells in vitro, but more effective against all tumor models tested (P388 leukemia, Gross leukemia, MS-2 sarcoma). The binding to the polypeptide markedly reduced drug toxicity but only slightly decreased drug potency. The daunorubicin-poly-L-aspartic acid conjugate demonstrated antitumor activity comparable to that of doxorubicin in leukemia models, but superior to that of doxorubicin in a solid tumor model (MS-2 sarcoma).

Pretreatment of Swiss mice and Sprague-Dawley rats with glutathione (GSH) reduced the acute lethal toxicity of cis-dichlorodiammine platinum (II) (cis-DDP) in a dose-dependent manner. The protection was accompanied by reduction of both body weight loss and by reduction of nephrotoxicity, as measured by a rise in serum blood urea nitrogen (BUN), creatinine levels and by histopathologic changes, which occurred 4 days following cis-DDP treatment. The antitumor effects of cis-DDP on experimental tumor models (P388 and Gross leukemia) were not significantly altered by GSH treatment. It is suggested that the partial protection by GSH from acute toxicity of the antitumor drug is directly related to protection of renal function.

Daunorubicin was covalently linked to poly-L-aspartic and poly-L-lysine of different molecular weights via the methylketone side-chain of the drug by the use of a method that employs the 14-bromo derivative of the antibiotic. During reaction ester and C-N linkages were formed with poly-L-aspartic acid and poly-L-lysine respectively. Whereas a reduction of drug toxicity was observed with both types of conjugate, only the linking to the anionic polymer produced an enhancement of drug activity. In contrast, when drug was covalently attached to poly-L-lysine, cytotoxic activity and in vivo potency and efficacy were markedly reduced. The different therapeutic properties of these conjugates can be explained in terms of the different nature and stability of chemical bonds formed between the drug and the amino groups and carboxyl functions of the polyamino acid carrier.

The therapeutic efficacy of photoradiation therapy (PRT) following hematoporphyrin derivative (HpD) administration was compared in the experimental MS-2 tumour model to that of conventional treatment methods for local control of neoplastic diseases. The therapeutic effects of PRT and surgical removal of primary tumour were comparable in these experiments. However, optimal effects were critically dependent on the stage of tumour development. In addition, the therapeutic advantage of PRT over radiotherapy suggest an interesting role of a new approach in tumours resistant to this conventional treatment.