Inhibition of alveolar bone loss by matrix metalloproteinase inhibitors in experimental periodontal disease

Periodontal disease is characterized by excessive host collagenase resulting in loss of gingival and periodontal ligament collagen and adjacent alveolar bone. Intragingival endotoxin injection induces a model of periodontal disease characterized by rapid bone loss with biochemical features similar to that of naturally occurring adult periodontitis. CH1766, a peptide with a zinc binding moeity which fits into the active site of the enzyme, and CH6631, a hydroxamic acid derivative with aryl-substituted sulphonamide residues, are inhibitors of matrix metalloproteinases (MMPIs) with differing inhibitory profiles as characterized by in vitro assays. In this study, endotoxin was injected into the gingivae of rats which were then treated orally with either 3 mg/kg or 30 mg/kg of one of the two inhibitory compounds. The gingival tissues were assessed for collagenase and gelatinase activity, plus three different pro-inflammatory cytokines. In addition, alveolar bone height in defleshed jaws was studied by computerized morphometric analysis and scanning electron microscopy. Both drugs reduced active and/or total MMP activity, in many cases to normal, and also partially normalized cytokine levels as well. A dose-response effect was seen with regard to amelioration of lipopolysaccharide-induced alveolar bone loss with both drugs. Other than studies with tetracyclines, this is the first report of beneficial effects of MMPIs in a model of periodontal disease, strongly suggesting that this class of agents could bring therapeutic benefit to patients with this disorder, and that periodontal disease can be used as a model to demonstrate in vivo efficacy of this class of drugs.     

Antibiotic resistance,virulence gene,and molecular profiles of Shiga toxin-producing Escherichia coli isolates from diverse sources in Calcutta,India

Antibiotic resistance, virulence gene, and molecular profiles of Shiga toxin-producing Escherichia coli (STEC) non-O157 strains isolated from human stool samples, cow stool samples, and beef samples over a period of 2 years in Calcutta, India, were determined. Resistance to one or more antibiotics was observed in 49.2% of the STEC strains, with some of the strains exhibiting multidrug resistance. The dominant combinations of virulence genes present in the strains studied were stx(1) and stx(2) (44.5% of strains) and stx(1), stx(2), and hlyA (enterohemorrhagic E. coli hemolysin gene) (19% of strains). Only 6.4% of the STEC strains harbored eae. The diversity of STEC strains from various sources was assessed by random amplification of polymorphic DNA (RAPD). STEC strains that gave identical or nearly similar DNA fingerprints in RAPD-PCR and had similar virulence genotypes were further characterized by pulsed-field gel electrophoresis (PFGE). Identical RAPD and PFGE profiles were observed in four sets of strains, with each set comprising two strains. There was no match in the RAPD and PFGE profiles between strains of STEC isolated from cows and those isolated from humans. It appears that the clones present in bovine sources are not transmitted to humans in the Calcutta setting although these strains showed evolutionary relatedness. Maybe for this reason, STEC has still not become a major problem in India.     

Excessive matrix metalloproteinase activity in diabetes: inhibition by tetracycline analogues with zinc reactivity

Diabetes mellitus in rats is characterized by excessive activity of several matrix metalloproteinases (MMPs), notably collagenase(s) and gelatinase(s), in skin, gingiva, and other tissues. A number of tetracyclines (TCs), both antimicrobial compounds as well as chemically modified non-antimicrobial TC analogues (CMTs) are known to possess potent inhibitory activity against these enzymes. Three conventional antimicrobial TCs and six CMTs were used in this study. In vitro, doxycycline was shown to possess higher inhibitory capacity (i.e. lower IC(max)) against diabetic rat skin collagenase than either minocycline or tetracycline HCl. Addition of excess zinc partially reversed the proteinase inhibition by TCs. In vivo, using rats made diabetic with streptozotocin (STZ), oral administration of various TCs led to decreased weight loss and substantial reductions in the activity of both skin collagenase and skin gelatinase (primarily MMP-9, 92 kDa) without affecting blood glucose. Using an in vitro spectrophotometric technique, the Zn(++) reactivity of several CMTs was assessed and found to be positively related to the potency of these compounds as MMP inhibitors. One particular CMT (CMT-5, pyrazole analogue), which is neither antimicrobial nor capable of binding metal cations, did not inhibit the MMPs. TCs have potential utility in management of diabetic complications mediated by excessive activity of MMPs.     

Orthodontic camouflage treatment of skeletal class II malocclusion with severe maxillary dentoalveolar protrusion

This case report describes the orthodontic treatment of a 14-year-old male patient who presented with prognathic maxilla, severe dentoalveolar proclination, deepbite and retained deciduous tooth. We selected headgear and fixed appliance to correct malocclusion but cooperation towards headgear was found less during treatment. So we chose orthodontic camouflage treatment to correct dentoalveolar problems without altering the skeletal base relation. The final treatment results were good and patient had improvement in esthetic and function.     

Intravenous regional sympatholysis: A double-blind comparison of guanethidine, reserpine, and normal saline

This double-blind, randomized study was designed to compare the effectiveness of intravenous regional sympatholysis using guanethidine, reserpine and normal saline. Twenty-one patients with reflex sympathetic dystrophy of an upper or lower extremity were enrolled and received intravenous regional blockade (IVRB) with one of the three medications. There was significant pain relief in all three groups at 30 min. There were no significant differences among the three groups in the degree of pain relief, the number of patients obtaining pain relief in the 30 min after the block, or the number of patients reporting more than 50% pain relief for more than 24 hr. The saline group's high rate of pain relief could be partially due to a mechanism of tourniquet-induced analgesia.     

Diagnostic epidural opioid technique

Diagnostic epidural blocks were performed on 27 chronic pain patients sequentially using saline, fentanyl, and lidocaine solution. The patients were divided into one of four groups based on their response to the epidural solutions: placebo response group--pain relief with placebo solutions; fentanyl response group--pain relief with epidural fentanyl; lidocaine response group (LRG)--pain relief with lidocaine but not fentanyl; and no response group--no pain relief with any of the solutions used. The four groups were compared on the basis of age, sex, site of pain, duration of pain, narcotic use, pain assessment index, and workmen's compensation claims. The comparisons resulted in the conclusion that LRG patients had a much longer average duration of pain than the other groups. On the basis of the information gathered, it was theorized that, despite their response to epidural lidocaine, LRG patients may actually be a group of operant pain patients. Their failure to receive analgesia from epidural fentanyl may be a learned response such that they associate any sensory input from the affected area as painful. If follow-up studies support these findings, then the diagnostic opioid technique may be a more sensitive tool in diagnosing chronic pain.     

Normative model for cold pressor test

The cold pressor test elicits an emotional/motivational pain experience from the immersion of a limb in cold water. It has been widely used to evaluate (experimental and chronic) pain. However, normative models for quantification and comparison for pain tolerance have not previously been established. This study developed a normative mathematical model for pain tolerance using the cold pressor test with over 600 subjects. Norms for age, sex, and ethnic group were calculated. In addition, chronic pain patients were compared with pain-free patients to determine normative differences in response. The results indicate that at any given age Anglo-Saxon males have the longest tolerance time followed by non-Anglo-Saxon males, Anglo-Saxon females, and finally non-Anglo-Saxon females. There is a consistent decrease in tolerance time as the male age increases and minimal change in tolerance time as the female age increases. Chronic pain patients exhibited the same type of pain response pattern as healthy volunteers when corrected for age, sex, and ethnocultural subgroup.     

Utility of coaxial technique for renal angioplasty in patients with a difficult-to-cross stenosis

The aim of this study was to evaluate the feasibility of coaxial approach in difficult-to-cross lesions in patients with failed percutaneous transluminal renal angioplasty by conventional over-the-wire exchange technique. Twelve stenoses in 10 patients (six women and four men; age range 19 ± 7 years) with uncontrolled hypertension were treated by this method. The stenosis was caused by nonspecific aortoarteritis in 8 patients and fibromuscular dysplasia in 2 patients. It was ostial in seven and post-ostial in five vessels. Conventional exchange technique was unsuccessful in all of them. All procedures were done by femoral route. Technical success was seen in 11 (92 %), without complication. The stenosis improved from 90 ± 2.1 % (range 80–100 %) to 6 ± 7 % (range 0–20 %), blood pressure decreased from 198 ± 12.3 mm Hg (range 180–220 mm Hg)/130 ± 6.7 mm Hg (range 120–140 mm Hg) to 119 ± 5.7 mm Hg (range 110–130 mm Hg)/83 ± 3.9 mm Hg (range 80–90 mm Hg), and number of drug treatments for hypertension fell from 3.6 ± 0.52 (range 3–4) to 1 ± 0.94 (range 0–3; p < 0.01). Percutaneous transluminal renal angioplasty resulted in “cure” in 3 patients and “improvement” in 7 patients. Follow-up period was 3–21 months (mean 6.4 months). No restenosis was detected. Coaxial approach is safe and effective in treating difficult-to-cross lesions in which renal angioplasty by conventional exchange technique is unsuccessful. Received: 7 May 1998; Revision received: 10 November 1998; Accepted: 25 November 1998     

Operative closure of patent ductus arteriosus in premature infants in the neonatal intensive care unit

Fifty-two premature infants underwent hemoclip closure of patent ductus arteriosus in the neonatal intensive care unit after a brief trial of fluid restriction and diuretics. Indomethacin was used in only four patients. The median time from diagnosis to operation was 3 days. There were no deaths directly attributable to operation. Nine operative complications developed in nine patients (17 percent). There were no surgical infections. Complications related to prematurity resulted in 20 deaths (38 percent). Patent ductus arteriosus closure in the neonatal intensive care unit prevented the complications of hypothermia, inadvertent extubation, and interruption of vascular access and monitoring. Early operative closure in the neonatal intensive care unit is the treatment of choice in most premature infants with patent ductus arteriosus.