Visualization of biodistribution of Zn complex with antidiabetic activity using semiconductor Compton camera GREI

Various types of zinc (Zn) complexes have been developed as promising antidiabetic agents in recent years. However, the pharmacological action of Zn complex is not elucidated because the biodistribution of the complex in a living organism has not been studied. Nuclear medicine imaging is superior technology for the noninvasive analysis of the temporal distribution of drug candidates in living organisms. Gamma-ray emission imaging (GREI), which was developed by our laboratory as a novel molecular imaging modality, was adopted to visualize various γ-ray–emitting radionuclides that are not detected by conventional imaging techniques such as positron emission tomography and single-photon emission computed tomography. Therefore, we applied GREI to a biodistribution assay of Zn complexes. In the present study, ⁶⁵Zn was produced in the ^natCu(p,n) reaction in an azimuthal varying field cyclotron for the GREI experiment. The distribution was then noninvasively visualized using GREI after the intravenous administration of a ⁶⁵Zn-labeled di(1-oxy-2-pyridinethiolato)zinc [Zn(opt)₂], ZnCl₂, and di(l-histidinato)zinc. The GREI images were validated using conventional invasive assays. This novel study showed that GREI is a powerful tool for the biodistribution analysis of antidiabetic Zn complexes in a living organism. In addition, accumulation of ⁶⁵Zn in the cardiac blood pool was observed for [Zn(opt)₂], which exhibits potent antidiabetic activity. These results suggest that the slow elimination of Zn from the blood is correlated to the antidiabetic activity of [Zn(opt)₂].     

Comprehensive Expression of Wnt Signaling Pathway Genes during Development and Maturation of the Mouse Cochlea

Background

In the inner ear Wnt signaling is necessary for proliferation, cell fate determination, growth of the cochlear duct, polarized orientation of stereociliary bundles, differentiation of the periotic mesenchyme, and homeostasis of the stria vascularis. In neonatal tissue Wnt signaling can drive proliferation of cells in the sensory region, suggesting that Wnt signaling could be used to regenerate the sensory epithelium in the damaged adult inner ear. Manipulation of Wnt signaling for regeneration will require an understanding of the dynamics of Wnt pathway gene expression in the ear. We present a comprehensive screen for 84 Wnt signaling related genes across four developmental and postnatal time points.

Results

We identified 72 Wnt related genes expressed in the inner ear on embryonic day (E) 12.5, postnatal day (P) 0, P6 and P30. These genes included secreted Wnts, Wnt antagonists, intracellular components of canonical signaling and components of non-canonical signaling/planar cell polarity.

Conclusion

A large number of Wnt signaling molecules were dynamically expressed during cochlear development and in the early postnatal period, suggesting complex regulation of Wnt transduction. The data revealed several potential key regulators for further study.     

Visceral Fat Accumulation,Insulin Resistance,and Elevated Depressive Symptoms in Middle-Aged Japanese Men

Objective

To investigate visceral fat accumulation and markers of insulin resistance in relation to elevated depressive symptoms (EDS).

Methods

Participants were 4,333 male employees (mean age, 49.3 years) who underwent abdominal computed tomography scanning, measured fasting insulin, and did not self-report diabetes and mental disorders under treatment and history of cancer, myocardial infarction, and stroke. Multivariable logistic regression was used to assess the association of EDS with abdominal fat deposition and markers of insulin resistance.

Results

Visceral fat area (VFA) and fasting insulin were significantly, positively associated with EDS. Multivariable-adjusted odds ratios (95% confidence interval) of high VFA for the lowest through highest quartile of depression score were 1 (reference), 1.18 (0.97–1.42), 1.25 (1.02–1.54), 1.23 (1.01–1.51), respectively, and corresponding figures for high fasting insulin were 1 (reference), 0.98 (0.80–1.19), 1.12 (0.91–1.38), and 1.29 (1.06–1.57), respectively. Subcutaneous fat area was not associated with EDS.

Conclusions

Results suggest that EDS is related to visceral, but not subcutaneous, fat accumulation and insulin resistance in middle-aged Japanese men.     

A new case of familial hyperproinsulinemia

We reported a case with increased serum immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR). The molar ratio of IRI to CPR was also increased. The propositus was diabetic with background retinopathy and neuropathy. No antibody to insulin or insulin receptor was detected in his serum and his insulin resistance was not so remarkable. When the serum was fractionated by gel filtration, about 90% of total IRI was recovered in the fraction where biosynthetic human proinsulin was eluted. The major part of the CPR was also recovered in the same fraction as proinsulin-like material. His daughter, 28 years old, a non-obese female, also had high IRI, CPR and a high molar ratio of IRI to CPR. A gel filtration study demonstrated the same elution profile as the propositus. Tryptic digestion failed to convert the proinsulin-like material from the propositus to insulin in a sufficient quantity to convert human proinsulin to insulin. These data strongly suggest that this family is a new case of familial hyperproinsulinemia, and the defect resides in the proinsulin molecule, not in the converting enzymes.     

Isoasparagine as a marker amino acid in the taxonomy of Characeae

Fourteen species of Characeae were analyzed for their free amino acids. This study, in combination with previous results (Sakanoet al., 1984) showed that all the species that belong to the generaChara (6 species),Lamprothamnium (1 species),Nitellopsis (1 species),Lychnothammus (1 species) and 5Nitella species of the members of the subsectionAnarthrodactylae contained a large amount of isoasparagine. In contrast, no isoasparagine was found in the species belonging toTolypella (3 species) and otherNitella (7 species). Presence of isoasparagine in some species of Characeae (N. flexillis andNitellopsis obtusa) was found to be independent of their localities (Japan, Canada and England). Species lacking isoasparagine (N. oligogyra and N. axilliformis) did not produce isoasparagine even under the condition that induced a great increase of this amino acid in the species that contained it (C. corallina andN. flexilis). These results indicate that isoasparagine is a distinct taxonomic marker and suggest that theNitella species of the subsectionAnarthrodactylae are the most primitive group inNitelleae in that they share synthesis and accumulation of isoasparagine withChareae and, hence, support the view (Kasaki, 1964) that the subsection may be treated as an independent genus.     

‘Males second’ strategy in the allocation of sexes by the parasitic wasp,Gryon japonicum

Summary Patterns of the sex ratio allocation of Gryon japonicum (Ashmead) (Hymenoptera: Scelionidae), a solitary egg parasitoid of Riptortus clavatus (Thunberg) (Heteroptera: Alydidae), were investigated in the laboratory, and the result was checked against the field data on the sex composition of the parasitoid. When five host eggs were presented simultaneously to each of the females of G. japonicum in a laboratory experiment, they had a strong tendency to lay a male egg in second host egg and female eggs in the others. However, when four host eggs were presented to each female more than 3 h after the completion of oviposition on a host egg, most of the females laid male eggs in the third oviposition, i.e. the second host eggs after the experimental interruption of oviposition. These results indicated that there was a mechanism for G. japonicum to produce a male egg in the second host egg in consecutive ovipositions, and that the mechanism was reset by more than 3 h intervals of oviposition. By this mechanism, G. japonicum is thought to produce the precise sex ratio in response to the size of a host egg batch. Field data on the size of a host egg batch and the sex composition of the parasitoid in a host egg batch supported this view.     

Identification and quantification of juvenile hormones from different developmental stages of the cockroach Nauphoetacinerea

By the combined use of high-pressure liquid chromatography, $\text{Galleria}$ bioassay and gas chromatography/ chemical ionization/mass spectrometry we were able to isolate and identify the three known natural juvenile hormones (JHs) from haemolymph extracts of larval and adult females of the cockroach $\text{Nauphoeta}$$\text{cinerea}$. This is the first demonstration of the simultaneous occurrence of the three JHs in the same insect and the first time JH I and II have been identified in a hemimetabolous insect. Quantitative investigations show that the composition of the three JHs is different at different developmental stages. The haemolymph of larvae contains a high percentage of JH I and II, whereas the haemolymph of adult females in the oocyte maturation stage contains mostly JH III. This suggests more juvenilizing functions for JH I and II and more gonadotropic functions for JH III.     

Chiasma studies in structural hybrids IX. Crossing-over in pericentric inversion ofScilla scilloides

InScilla scilloides (Lindle) Druce, the heterozygotes for a pericentric inversion were found to be predominant in a small natural population consisting of cytogenetic type BB (2n=18). Pericentric inversion may include about half the length of the original subtelocentric chromosome, changing it to submetacentric. The 9II were always formed in these heterozygotes as well as in normal plants at MI in PMCs. A single chiasma was formed in the shorter one of two inverted segments divided by the kinetochore at MI, while one or two inversion chiasmata were observed in the longer segment. The AI separation was always regular. Since both arms of a normal chromosome and those of an inverted one were clearly distinguishable from one another at AI and AII, two kinds of crossover chromatids could be identified. Both sides of the single inversion chiasma always opened out reductionally. The frequency of bivalent without inversion chiasma agreed statistically with that of half-bivalent at AI or chromatid structure at AII, which resulted from non crossing-over within the inverted segment. Likewise, no statistical difference was found between the frequency of a single chiasma and that of a single crossing-over product in a longer inverted segment. These findings have clearly proved that the chiasma is a consequence of genetic crossing-over. The average proportion of good pollen grains in the inversion heterozygotes, 53.6%, amounted to about half that of normal plants, 97.7%.