Detection of stunned myocardium in post-reperfusion cases of acute myocardial infarction

OBJECTIVE: This study was designed to evaluate the correlation between improvements in serial images obtained by SPECT imaging with Tc-99m MIBI (MIBI) and I-123 BMIPP (BMIPP) and the recovery of cardiac function in acute myocardial infarction (AMI) patients after reperfusion therapy. METHODS: Twenty five patients who were admitted to the emergency room within 24 hours after the onset of the first event of AMI were enrolled in this study. The culprit coronary arteries were identified by CAG and were treated with direct percutaneous transluminal coronary angiography (PTCA), followed by stent implantation. To determine risk areas, initial image at the onset was acquired by the freeze method, in which MIBI was injected before the treatment and the image was collected after the reperfusion therapy. After the reperfusion treatment was completed, MIBI SPECT images at rest were performed on days 7 and 60. Both early and late images, including gated SPECT images were acquired after 30-60 minutes and 6 hours post injection, respectively. In addition, BMIPP SPECT images at rest were obtained 30 minutes after injection of 148 MBq BMIPP on days 7 and 60 (BMIPP image). The obtained image was divided into 48 segments and percent uptake of each segment was calculated. The number of abnormal areas (NAA) was defined as the segment with a % uptake less than 60% of normal uptake, and the change of NAA over time was evaluated. RESULTS: The NAA on the MIBI-early image significantly improved between thepre image and the day 7 image (p < 0.001), but no similar improvement was observed between day 7 and day 60. On the other hand, the NAA of the MIBI-delayed image did not significantly improve up to day 7, but a slight improvement was observed on days 7 and 60 (p < 0.05). A significant improvement in the NAA of the BMIPP image was observed between day 7 and day 60, as shown in the delayed image (p < 0.05). An excellent correlation on the NAA between the MIBI-delayed image and the BMIPP image was observed with r = 0.983 (p < 0.001) at day 7 and r = 0.984 (p < 0.001) at day 60 resulting in a consistent diagnosis. Analysis of the myocardial function by means of gated SPECT indicated that the wall motion significantly improved as the myocardial perfusion improved up to day 7 and thereafter a steady improvement was observed up to day 60. The improvement in the NAA in MIBI-delayed images in the subacute phase (day 7) and in the chronic phase (day 60) as well as BMIPP images showed excellent correlation with the improvement in RWM and RWT (MIBI-delayed image: r = 0.550 (RWM), r = 0.647 (RWT)), (BMIPP image: r = 0.536 (RWM), r = 0.565 (RWT)). CONCLUSION: We conclude that insufficient ATP production caused by mitochondrial dysfunction in stunned myocardium is closely related to MIBI delayed and BMIPP image Furthermore, MIBI delayed imaging as well as BMIPP imaging will provide a clue to the state of stunned myocardium after reperfusion therapy in patients with AMI.     

Pretreatment with 8-methoxypsoralen, a potent human CYP2A6 inhibitor, strongly inhibits lung tumorigenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in female A/J mice

Human CYP2A6 has been recognized as being involved in the mutagenic activation of promutagens such as the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Methoxsalen (8-methoxypsoralen) was reported to inhibit CYP2A6. In the present study, the inhibitory effects of methoxsalen on NNK-induced lung tumorigenesis in female A/J mice were examined. Female A/J mice were treated with methoxsalen at doses of 50 or 12.5 mg/kg body weight, given by stomach tube, daily for 3 days. One h after the final treatment, NNK was injected i.p. at a dose of 2 mg/mouse. The experiments were terminated 16 weeks after the first methoxsalen treatment, and lung adenomas were analyzed. Pretreatment of methoxsalen significantly reduced tumor incidence from 93.8% to 16.7% (50 mg/kg) and 20.0% (12.5 mg/kg), and tumor multiplicity from 5.97 to 0.23 (50 mg/kg) and 0.25 (12.5 mg/kg) tumors/mouse. These results clearly demonstrated that methoxsalen, a potent human CYP2A6 inhibitor, is a strong chemopreventive agent against NNK-induction of lung tumorigenesis.     

Combined effects of prostaglandin E receptor subtype EP1 and subtype EP4 antagonists on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice

Previous studies have shown that prostaglandin E₂ (PGE₂) is involved in intestinal carcinogenesis through its binding to the PGE₂ receptor subtypes EP₁ and EP₄ and activation of downstream pathways. ONO-8711 and ONO-AE2–227, prostaglandin E receptor subtype EP₁- and EP₄-selective antagonists, respectively, are known to suppress formation of intestinal polyps in adenomatous polyposis coli gene-deficient mice. The present study was designed to investigate the combined effects of EP₁ and EP₄ antagonists on spontaneous polyp formation in APC1309 mice in order to determine the contribution of each receptor to intestinal tumorigenesis. APC1309 mice were treated with 400 ppm of ONO-8711 alone, 400 ppm of ONO-AE2–227 alone or both in combination in the diet for 6 weeks. The mean area of polyps found in the intestine, calculated as the longer diameter × the shorter diameter ×π, was reduced by 12%, 43% (P<0.01) and 56% (P<0.01) of the mean control value (8.8 mm²) in the ONO-8711 alone, ONO-AE2–227 alone and combination treatment groups, respectively, suggesting clear additive effects of the combination. The same additive tendency for suppression was also observed with respect to the numbers of polyps in the intestine. Polyp size reduction was more remarkable with the EP₄ antagonist, while the number reduction was more pronounced with the EP₁ antagonist. Our results indicate that EP₁ and EP₄ may have separate intrinsic roles and, to some extent, contribute to polyp formation independently. Thus, combination treatment has potential for the chemoprevention of colon carcinogenesis.     

Changes in urinary NTX levels in patients with primary osteoporosis undergoing long-term bisphosphonate treatment

BACKGROUND: Bisphosphonates, antiresorptive drugs, are widely used to treat osteoporosis patients. However, recent reports indicated that several osteoporosis patients who underwent long-term bisphosphonate therapy subsequently developed severe suppression of bone turnover. We investigated whether urinary crosslinked N-telopeptide of type I collagen (NTX), a bone resorption marker, in osteoporosis patients was highly suppressed during long-term treatment with alendronate or risedronate. METHODS: We investigated 87 primary osteoporosis outpatients who were treated with alendronate or risedronate for more than 2 years. All patients were women, with an average age of 72.6 years. Altogether, 49 patients were treated with alendronate and 38 with risedronate, and the average administration period was 3.5 years. We defined high suppression as NTX being reduced <9.3 nmol bone collagen equivalent/mmol.Cr and a 35% decrease from baseline. RESULTS: In total, 11 of 87 patients (12.6%) had high NTX suppression based on the above criteria. The incidences of high suppression of NTX at 1,2,3,and 4 years after starting the treatment were 0%, 1.1%, 11.9%, and 4.7%, respectively. The average age, bone mineral density, and NTX values at baseline and the administration period were not associated with high suppression of NTX during alendronate or risedronate treatment. Regarding suppression of NTX during long-term treatment, there was no significant difference between alendronate and risedronate. CONCLUSIONS: The results suggested that long-term treatment with bisphosphonates necessitates careful follow-up of the patients.     

Psychiatric disorders following and preceding temporal lobectomy]

We analysed pre- as well as post-operative psychiatric disorders in thirty eight patients with temporal lobe epilepsy. While postoperative paranoid disorders were closely correlated with preoperative acute interictal psychoses, episodes of postictal psychoses prior to surgery were associated with postoperative mood disorders. A good prognosis of postoperative mood disorders was stressed. The literature search supported the predominance of right-sided lobectomy in patients with de novo psychoses after surgery. The relationship between left-sided lobectomy and postoperative mood disorders needs further amplification and remains tentative. We stressed the need for a prophylactic psychotherapy to surgical candidates to cope with unrealistic wishes to get relieved from all the difficulties in their lives after temporal lobectomy.     

Effect of protoporphyrin IX on the induction of respiratory impairment of hepatic mitochondria by carbon tetrachloride in rats]

The effect of pretreatment with protoporphyrin IX (PP) on the impairment of hepatic mitochondrial respiration induced by carbon tetrachloride (CCl4) was studied in rats. Treatment of animals intraperitoneally with CCl4 resulted in marked impairment of states 4 and 3 respirations, respiratory control and oxidative phosphorylation of mitochondria in the presence of succinate, beta-hydroxybutyrate or glutamate as substrates. The PP, given intravenously, caused no alterations in those mitochondrial functions. The treatment with PP prior to the administration of CCl4 inhibited the induction of mitochondrial respiratory impairment by CCl4. CCl4 increased markedly the contents of lipid peroxide in the liver but not those in the mitochondria. The increase of hepatic lipid peroxides by CCl4 was markedly reduced by the pretreatment with PP. These results indicate that PP effectively protects the mitochondria from the functional disorder caused by CCl4.     

A case of attempted suicide from the ingestion of formalin

The ingestion of formalin causes disorders in the oral cavity, the gastrointestinal tract, liver, kidney, lung, heart, and central nervous system in the early phase of reaction. The stomach suffers the most severe damage in such cases because the formalin is in contact with the gastric mucosa longer than in the other parts of the gastrointestinal tract. Gastric ulcers and mild hemorrhaging are frequently seen. There are no reported cases of gastric perforations in Japan (n= 15), and there are only two reported cases in other countries since 1950 (n = 11). The ingestion of formalin could lead to peritonitis without perforation because of gastric wall inflammation. Cicatrical stricture of the stomach tends to be a major problem in the late phase of formalin ingestion. Similar to our case, seven of twelve reported cases of cicatrical deformity survived without operation. Therefore, a gastrectomy for the cicatrical deformity might not be always indicated if the patients are able to feed themselves sufficiently or if parenteral nutrition can be provided.