We used an experimental model in the rat to examine the effects of long-term treatment with crocin, a glycosylated carotenoid from the stigmas of the saffron crocus, on colon cancer. BD-IX rats were divided into four groups: Groups G1 and G2, designated "cancer groups," were used to study the effects of crocin on the progression of colon cancer, and Groups G3 and G4, designated "toxicity groups," were used to study the effects of the treatment on metabolic processes and the parenchyma. DHD/K12-PROb cells were injected subcutaneously into the chest of Group G1 and G2 animals. From 1 to 13 weeks after inoculation, animals in Groups G2 and G4 received a weekly injection of crocin (400 mg/kg body wt s.c.). Animals in Groups G1 and G3 received no treatment. In addition, lines of animal and human colon adenocarcinoma cells (DHD/K12-PROb and HT-29) were used to perform assays in vitro to examine the cytotoxicity of crocin. Life span was extended and tumor growth was slower in crocin-treated female rats, but no significant antitumor effect was found in male rats. Acute tubular necrosis was found in all kidney samples from crocin-treated animals, but slight signs of nephrotoxicity were found by biochemical analysis of the serum. In assays in vitro, crocin had a potent cytotoxic effect on human and animal adenocarcinoma cells (HT-29 and DHD/K12-PROb cells, 50% lethal dose = 0.4 and 1.0 mM, respectively). Treated cells exhibited a remarkable loss of cytoplasm and wide cytoplasmic vacuole-like areas. In conclusion, long-term treatment with crocin enhances survival selectively in female rats with colon cancer without major toxic effects. The effects of crocin might be related to its strong cytotoxic effect on cultured tumor cells.

Adenocarcinoma↗

PubMed1998

Subtotal colectomy vs. intraoperative colonic irrigation in the management of obstructed left colon carcinoma.

PURPOSE: Whether primary anastomosis should be performed after segmental resection with intraoperative colonic irrigation or subtotal colectomy is not yet established in the surgical treatment of obstructive left colon carcinoma. In this prospective, nonrandomized study, we present the results of 66 patients undergoing one-stage surgery for obstructed left colon carcinoma. PATIENTS AND METHODS: We compared two techniques, subtotal colectomy (35 patients) and intraoperative colonic irrigation with segmental resection and immediate anastomosis (31 patients). RESULTS: The mortality rate was similar in both groups, 8.5 percent in the subtotal colectomy group and 3.2 percent in the intraoperative colonic irrigation group. The surgical complication rate was significantly higher in the intraoperative colonic irrigation group (41.9 percent) than in the subtotal colectomy group (14.2 percent; P < 0.05). Mean operating time was significantly lower in the subtotal colectomy group than in the intraoperative colonic irrigation group (P < 0.05). Both groups had a similar mean duration of hospital stay. Ten patients who underwent subtotal colectomy (31.2 percent) presented with diarrhea in the immediate postoperative period, which disappeared spontaneously or with antidiarrheal medication; a disabling diarrhea persisted in two patients only (6.2 percent). CONCLUSION: We believe that subtotal colectomy is the treatment of choice for obstructed left-sided colonic carcinoma. Segmental resection with intraoperative colonic irrigation is more appropriate than subtotal colectomy only in patients with carcinomas of the rectosigmoid junction or with previous anal incontinence to avoid the appearance of postoperative diarrhea.

Adult↗

PubMed1997

Surgical treatment of lung metastases of head and neck tumors.

BACKGROUND: Head and neck tumors often spread to the lungs, with a variety of presentations. The ideal treatment for those patients is still controversial. Resection of lung metastases was shown to significantly influence overall survival of patients. OBJECTIVE: To evaluate results of surgical resection of lung nodules in patients with head and neck primary tumors. METHODS: A retrospective analysis was made of 53 patients with head and neck tumors and lung nodules (no other metastases detected in other organs) admitted to our department. They were separated into two groups: OPER (thoracotomy, n = 26), and NOTOPER (no thoracotomies, n = 27). Overall survival was compared (Kaplan-Meier, log-rank) between groups. RESULTS: Overall median survival of all patients was 10 months, of OPER 20 months, and of NOTOPER 6 months (P <0.0001). Complete resection (n = 19) of lung metastases was associated with the greatest survival rate (median 23 months). Patients submitted to incomplete resection (n = 7) had a median survival of 16 months, compared with 7 months for patients who received only chemotherapy (n = 7) and 4 months for patients (n = 20) with no treatment (P <0.0001). CONCLUSION: Resection of lung metastases offers a significant survival benefit for patients with head and neck primary tumors, when compared with the current chemotherapeutic regimens. It should be considered for all patients clinically fit and who present with no extrapulmonary disease.

Female↗

PubMed1997

Identification of the HSV-1 genome by "Dot Blot hybridization" in the geniculate ganglion of rabbits.

Herpes simplex Virus type 1 (HSV-1) was inoculated into 48 rabbits by 3 different routes: 10 rabbits were dosed by mouth, 18 rabbits injected in the tongue and 14 injected in the perineurium of the facial nerve at its entrance into the stylomastoid foramen. Some of the animals were killed after a week and others after three weeks. Facial palsy was produced in none of the cases. Seroconversion was demonstrated in the peripheral blood of 100% of the inoculated animals. Cultures of macerate of the facial nerve and geniculate ganglion, as well as of the ipsilateral medulla, were negative. DNA from HSV-1 was found by "Dot Blot hybridization" technique in 30% of the macerates of the geniculate ganglion and facial nerve and in 60% of the medulla macerate in those animals killed after one week and in 0% of both samples in those killed in the third week. The fact that the HSV-1 could be isolated in the geniculate ganglion of the facial nerve continues to support the possibility of this virus as the causal agent for facial palsy, either as a single disease or associated with other symptoms.

Animals↗

PubMed1996

Design, synthesis, and biological evaluation of ellipticine-estradiol conjugates.

Three ellipticine-estradiol conjugates were synthesized in an effort to target the cytotoxicity of ellipticine to estrogen-receptor positive cells. The three conjugates were prepared with linker chains extending from the 17 alpha position of the estradiol to N-2 (compound 3), N-6 (compound 4), and C-9 (compound 5) positions of ellipticine. The ellipticine-estradiol conjugates were evaluated for their abilities to bind to estrogen receptors, to inhibit topoisomerase II, and for their cytotoxicities in human cancer cell lines. Conjugates 3 and 5 displayed weak binding affinities of 0.132 and 0.303 for the estrogen receptor (relative to estradiol = 100), while conjugate 4 did not show any detectable binding to the estrogen receptor. Compound 3 was a moderate inhibitor of topoisomerase II (IC50 24.1 microM), while 4 and 5 were inactive. Conjugate 3 was consistently more cytotoxic (GI50 values 1-10 microM) than compounds 4 and 5 (GI50 values 10-100 microM) in a variety of human cancer cell lines. None of the compounds displayed any selectivity for estrogen-receptor positive cell lines, which probably reflects their weak affinities for estrogen receptors.

Antineoplastic Agents↗

PubMed1996

Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro.

Extracts of saffron (Crocus sativus L.) have been reported to inhibit cell growth of human tumor cells. In order to study the cytotoxic effect of the characteristic compounds of saffron spice, we have isolated crocin, crocetin, picrocrocin and safranal. Doses inducing 50% cell growth inhibition (LD50) on HeLa cells were 2.3 mg/ml for an ethanolic extract of saffron dry stigmas, 3 mM for crocin, 0.8 mM for safranal and 3 mM for picrocrocin. Crocetin did not show cytotoxic effect. Cells treated with crocin exhibited wide cytoplasmic vacuole-like areas, reduced cytoplasm, cell shrinkage and pyknotic nuclei, suggesting apoptosis induction. Considering its water-solubility and high inhibitory growth effect, crocin is the more promising saffron compound to be assayed as a cancer therapeutic agent.

Antineoplastic Agents, Phytogenic↗

PubMed1996

Castleman's disease restricted to the infratemporal fossa.

Giant lymph node hyperplasia (Castleman's disease) is usually reported as a solitary mediastinal tumour, although involvement of other anatomical sites and a multicentric form have been reported. We describe a rare case of Castleman's disease due to its localisation (the left infratemporal fossa) and histology (plasma-cell variant). A brief review of the main clinico-histological characteristics of Castleman's disease is also presented.

Brain↗

PubMed1996

Biliary secretion in suckling goats: the effect of maternal milk and of a lamb milk replacer.

A total of 45 preruminant goats were fed either goat milk or a milk substitute. The postnatal development of bile secretion and biliary lipids composition of suckling goats and the influence upon these parameters of maternal milk substitution were studied during the first month of life. Samples of hepatic and gallbladder bile were obtained from kids of 1, 7, 14, 21 and 28 day-old. Bile flow rate, cholesterol, total bile salts and phospholipids were measured. Our results show that the quality of the protein and fat used in the elaboration of the milk replacer, affects the evolution of both hepatic bile flow and biliary lipids composition. Differences between gallbladder and hepatic bile composition show a scarce concentration capacity of the gallbladder with both diets and at all ages studied.

Animals↗

PubMed1996

Complications of supraglottic laryngectomy for carcinomas of the supraglottis and the base of the tongue.

The medical records of patients with either a supraglottic carcinoma (n = 193) or a base of tongue carcinoma (n = 56) who underwent a supraglottic laryngectomy were studied. Because of aspiration total laryngectomy was required in 9.8% and 21.4% of patients with supraglottic and base of tongue carcinomas, respectively, being related to locally advanced stage of disease in the base of tongue and to an age older than 65 years in the case of supraglottic carcinomas. The non-decannulation rates were 23.8% and 50% in supraglottic and base of tongue tumours respectively. Post-operative radiotherapy did not influence the decannulation rate, but advanced local disease and age did. Post-operative mortality in the first month after the operation was 2.6% in supraglottic tumours and 3.6% in base of tongue tumours.

Adult↗

PubMed1996

Impairments of the protein C system and fibrinolysis in infection-associated stroke.

BACKGROUND AND PURPOSE: Infection/inflammation appears to be an important predisposing risk factor for brain infarction, but little is known regarding underlying molecular mechanisms. We examined the hypothesis that patients with brain infarction preceded by infection/inflammation within 1 week could be identified by a distinctive procoagulant laboratory profile characterized by abnormalities in the protein C system and endogenous fibrinolysis. METHODS: We performed a case-control study examining the relationship between preceding systemic infectious/inflammatory syndromes and selected immunohematologic variables in 36 patients with acute brain infarction and 81 control subjects (community control subjects [n = 47] and hospitalized nonstroke neurological patient controls [n = 34]). RESULTS: The stroke group had a lower mean level of the circulating antithrombotic enzyme activated protein C (APC) (4.33 +/- 0.34% [log-transformed percentage of control value, mean +/- SD]) than community control subjects (4.51 +/- 0.27%, P < .02) or hospitalized neurological patient controls (4.57 +/- 0.31%, P < .005). The lowest circulating APC levels were found in the stroke group with antecedent infection/inflammation within 1 week preceding index brain infarction (4.23 +/- 0.4%, n = 12). Within the stroke group, circulating APC levels were inversely related to IgG isotype anticardiolipin antibody titers (r = -.55, P < .001). Only the stroke group with infection/inflammation within 1 week had elevated plasma C4b binding protein compared with control subjects (141 +/- 61% versus 112 +/- 44%, P < .05). Stroke patients with antecedent infection/inflammation had a distinctively lower ratio of active tissue plasminogen activator to plasminogen activator inhibitor (0.11 +/- 0.04, n = 9) than other stroke patients (0.19 +/- 0.06, n = 9, P < .01) and control subjects (0.22 +/- 0.16, n = 17, P < .02). CONCLUSIONS: Impairments in the protein C pathway and endogenous fibrinolysis may contribute to the increased risk for brain infarction after recent (< or = 1 week) infection/inflammation. A decrease in the circulating anticoagulant APC may be related to elevated antiphospholipid antibody titers.

Antibodies, Anticardiolipin↗

PubMed1996

Activated protein C resistance in ischemic stroke not due to factor V arginine506-->glutamine mutation.

BACKGROUND AND PURPOSE: Resistance to activated protein C (APC), a natural plasma anticoagulant, is the most common identifiable risk factor for venous thromboembolic disease. One point mutation in coagulation factor V that renders it APC-resistant is found in >90% of APC-resistant venous thrombosis patients. To determine the prevalence of APC resistance and of this factor V mutation in stroke, we screened a group of ischemic stroke patients. METHODS: Hispanic ischemic stroke patients were screened using two different activated partial thromboplastin time-based assays. One assay using neat patient plasma determined APC resistance, and the other assay using patient plasma diluted into factor V-deficient plasma determined APC-resistant factor V, including the Arg506-->Gln mutation. Results were compared with those in 31 Hispanic control subjects of similar ages. RESULTS: Six of 63 (9.5%) stroke patients had APC resistance compared with none of 31 (0%) control subjects. No patient or control subject had APC-resistant factor V, ie, the factor V Arg506-->Gln mutation. CONCLUSIONS: In Hispanic patients with ischemic stroke, the incidence (approximately 10%) of APC resistance is not caused by the factor V Arg506-->Gln mutation. APC resistance not caused by this factor V mutation may be a risk factor for ischemic stroke in this population.

Arginine↗

PubMed1996

Anaphylactic reaction to rocuronium bromide.

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Abdominal Pain↗

PubMed1996

Synthesis of a series of cytotoxic 2-acyl-1,2-dihydroellipticines which inhibit topoisomerase II.

An array of novel 2-acyl-1,2-dihydroellipticines was prepared and evaluated for in vitro cytotoxicity in a variety of human cancer cell lines. The ellipticine analogs were also tested for inhibition of topoisomerase II in both decatenation and cleavable complex formation assays. Some of the new ellipticine derivatives were prepared by acylation of ellipticine with acid chlorides in tetrahydrofuran, followed by reduction of the intermediate 2-acylellipticinium ions with sodium cyanoborohydride. Others were synthesized by acylation of ellipticine with p-nitrophenyl chloroformate, reduction of the 2-acylellipticinium ion with sodium cyanoborohydride, and displacement of the p-nitrophenoxide anion with a variety of oxygen and nitrogen nucleophiles. The cytotoxicities of the new 2-acyl-1,2-dihydroellipticines varied widely, and correlated well with their topoisomerase II inhibitory activities.

Antineoplastic Agents, Phytogenic↗

PubMed1995

Identification of candidate residues for interaction of protein S with C4b binding protein and activated protein C.

Protein S is a plasma factor essential for prevention of thrombosis, partly due to its activity as a cofactor for the plasma anticoagulant protease-activated protein C. To expand knowledge about structure-function relationships in homologous protein S molecules, studies of protein S from different species have been performed. Protein S anti-coagulant activity in human, monkey, bovine, and porcine plasma has been inactivated by purified human C4b binding protein (C4BP) with dose-dependence, suggesting that each protein S can bind human C4BP and that only the free form of each is anti-coagulantly active. Purified porcine protein S has a 10-fold higher Kd for human C4BP than has human protein S. Protein S residues 420-434 provide an essential binding site for the negative regulator C4BP. cDNA sequences show that protein S residues 420-434 are highly conserved in all four species with the notable exception of Lys-429-Ile in porcine protein S. Differences between porcine and human protein S, e.g. Lys-429-Ile, Lys-43-Ala, Ser-197-Leu, Ser 199-Phe, Glu-463-Gly, Lys-571-Glu, Asn-602-Ile, Gln-607-Pro, may contribute to the decreased affinity of porcine protein S for human C4BP. Moreover, the species specificity of cofactor activities of various species of protein S is determined for human versus bovine-activated protein C, and these results, combined with sequence comparisons, agree with previous evidence that the thrombin-sensitive region and the first epidermal growth factor domain of protein S, i.e. residues 47-116, are responsible for recognition of activated protein C.

Amino Acid Sequence↗